Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus
Identifieur interne : 000731 ( Pmc/Checkpoint ); précédent : 000730; suivant : 000732Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus
Auteurs : Tiziano Donnarumma [Royaume-Uni] ; George R. Young [Royaume-Uni] ; Julia Merkenschlager [Royaume-Uni] ; Urszula Eksmond [Royaume-Uni] ; Nadine Bongard [Allemagne] ; Stephen L. Nutt [Australie] ; Claude Boyer [France] ; Ulf Dittmer [Allemagne] ; Vu Thuy Khanh Le-Trilling [Allemagne] ; Mirko Trilling [Allemagne] ; Wibke Bayer [Allemagne] ; George Kassiotis [Royaume-Uni]Source :
- Cell Reports [ 2211-1247 ] ; 2016.
Abstract
CD4+ T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8+ T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4+ T cells. However, the conditions that induce CD4+ CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)+ CD4+ CTLs, which distinguishes them from other CD4+ T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature. The balance between CD4+ CTL and Tfh differentiation heavily depends on the class of infecting virus and is jointly regulated by the Tfh-related transcription factors
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DOI: 10.1016/j.celrep.2016.10.013
PubMed: 27806296
PubMed Central: 5149578
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d'Azur</region></placeName></affiliation></author><author><name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen</wicri:regionArea><wicri:noRegion>45122 Essen</wicri:noRegion><wicri:noRegion>45122 Essen</wicri:noRegion><wicri:noRegion>45122 Essen</wicri:noRegion></affiliation></author><author><name sortKey="Le Trilling, Vu Thuy Khanh" sort="Le Trilling, Vu Thuy Khanh" uniqKey="Le Trilling V" first="Vu Thuy Khanh" last="Le-Trilling">Vu Thuy Khanh Le-Trilling</name><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany</nlm:aff><country 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first="George R." last="Young">George R. Young</name><affiliation wicri:level="1"><nlm:aff id="aff1">Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT</wicri:regionArea><wicri:noRegion>London NW1 1AT</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Retrovirus-Host Interactions, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Retrovirus-Host Interactions, The Francis Crick Institute, 1 Midland Road, London NW1 1AT</wicri:regionArea><wicri:noRegion>London NW1 1AT</wicri:noRegion></affiliation></author><author><name sortKey="Merkenschlager, Julia" sort="Merkenschlager, Julia" uniqKey="Merkenschlager J" first="Julia" last="Merkenschlager">Julia Merkenschlager</name><affiliation wicri:level="1"><nlm:aff id="aff1">Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT</wicri:regionArea><wicri:noRegion>London NW1 1AT</wicri:noRegion></affiliation></author><author><name sortKey="Eksmond, Urszula" sort="Eksmond, Urszula" uniqKey="Eksmond U" first="Urszula" last="Eksmond">Urszula Eksmond</name><affiliation wicri:level="1"><nlm:aff id="aff1">Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT</wicri:regionArea><wicri:noRegion>London NW1 1AT</wicri:noRegion></affiliation></author><author><name sortKey="Bongard, Nadine" sort="Bongard, Nadine" uniqKey="Bongard N" first="Nadine" last="Bongard">Nadine Bongard</name><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen</wicri:regionArea><wicri:noRegion>45122 Essen</wicri:noRegion><wicri:noRegion>45122 Essen</wicri:noRegion><wicri:noRegion>45122 Essen</wicri:noRegion></affiliation></author><author><name sortKey="Nutt, Stephen L" sort="Nutt, Stephen L" uniqKey="Nutt S" first="Stephen L." last="Nutt">Stephen L. Nutt</name><affiliation wicri:level="1"><nlm:aff id="aff5">The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052</wicri:regionArea><wicri:noRegion>VIC 3052</wicri:noRegion></affiliation></author><author><name sortKey="Boyer, Claude" sort="Boyer, Claude" uniqKey="Boyer C" first="Claude" last="Boyer">Claude Boyer</name><affiliation wicri:level="1"><nlm:aff id="aff6">Centre d’Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, UM2, Marseille 13288, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Centre d’Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, UM2, Marseille 13288</wicri:regionArea><wicri:noRegion>13288</wicri:noRegion><placeName><settlement type="city">Marseille</settlement><region type="région" nuts="2">Provence-Alpes-Côte d'Azur</region></placeName></affiliation></author><author><name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen</wicri:regionArea><wicri:noRegion>45122 Essen</wicri:noRegion><wicri:noRegion>45122 Essen</wicri:noRegion><wicri:noRegion>45122 Essen</wicri:noRegion></affiliation></author><author><name sortKey="Le Trilling, Vu Thuy Khanh" sort="Le Trilling, Vu Thuy Khanh" uniqKey="Le Trilling V" first="Vu Thuy Khanh" last="Le-Trilling">Vu Thuy Khanh Le-Trilling</name><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen</wicri:regionArea><wicri:noRegion>45122 Essen</wicri:noRegion><wicri:noRegion>45122 Essen</wicri:noRegion><wicri:noRegion>45122 Essen</wicri:noRegion></affiliation></author><author><name sortKey="Trilling, Mirko" sort="Trilling, Mirko" uniqKey="Trilling M" first="Mirko" last="Trilling">Mirko Trilling</name><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen</wicri:regionArea><wicri:noRegion>45122 Essen</wicri:noRegion><wicri:noRegion>45122 Essen</wicri:noRegion><wicri:noRegion>45122 Essen</wicri:noRegion></affiliation></author><author><name sortKey="Bayer, Wibke" sort="Bayer, Wibke" uniqKey="Bayer W" first="Wibke" last="Bayer">Wibke Bayer</name><affiliation wicri:level="1"><nlm:aff id="aff4">Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen</wicri:regionArea><wicri:noRegion>45122 Essen</wicri:noRegion><wicri:noRegion>45122 Essen</wicri:noRegion><wicri:noRegion>45122 Essen</wicri:noRegion></affiliation></author><author><name sortKey="Kassiotis, George" sort="Kassiotis, George" uniqKey="Kassiotis G" first="George" last="Kassiotis">George Kassiotis</name><affiliation wicri:level="1"><nlm:aff id="aff1">Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT</wicri:regionArea><wicri:noRegion>London NW1 1AT</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Medicine, Faculty of Medicine, Imperial College London, London W2 1PG, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Medicine, Faculty of Medicine, Imperial College London, London W2 1PG</wicri:regionArea><wicri:noRegion>London W2 1PG</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cell Reports</title><idno type="eISSN">2211-1247</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>CD4<sup>+</sup> T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8<sup>+</sup> T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4<sup>+</sup> T cells. However, the conditions that induce CD4<sup>+</sup> CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)<sup>+</sup> CD4<sup>+</sup> CTLs, which distinguishes them from other CD4<sup>+</sup> T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature. The balance between CD4<sup>+</sup> CTL and Tfh differentiation heavily depends on the class of infecting virus and is jointly regulated by the Tfh-related transcription factors <italic>Bcl6</italic> and <italic>Tcf7</italic> (encoding TCF-1) and by the expression of the inhibitory receptors PD-1 and LAG3. This unique profile of CD4<sup>+</sup> CTLs offers targets for their study, and its antagonism by the Tfh program separates CD4<sup>+</sup> T cells with either helper or killer functions.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Akhmetzyanova, I" uniqKey="Akhmetzyanova I">I. Akhmetzyanova</name></author><author><name sortKey="Zelinskyy, G" uniqKey="Zelinskyy G">G. Zelinskyy</name></author><author><name sortKey="Schimmer, S" uniqKey="Schimmer S">S. Schimmer</name></author><author><name sortKey="Brandau, S" uniqKey="Brandau S">S. Brandau</name></author><author><name sortKey="Altenhoff, P" uniqKey="Altenhoff P">P. Altenhoff</name></author><author><name sortKey="Sparwasser, T" uniqKey="Sparwasser T">T. Sparwasser</name></author><author><name sortKey="Dittmer, U" uniqKey="Dittmer U">U. Dittmer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Antunes, I" uniqKey="Antunes I">I. Antunes</name></author><author><name sortKey="Tolaini, M" uniqKey="Tolaini M">M. Tolaini</name></author><author><name sortKey="Kissenpfennig, A" uniqKey="Kissenpfennig A">A. Kissenpfennig</name></author><author><name sortKey="Iwashiro, M" uniqKey="Iwashiro M">M. Iwashiro</name></author><author><name sortKey="Kuribayashi, K" uniqKey="Kuribayashi K">K. Kuribayashi</name></author><author><name sortKey="Malissen, B" uniqKey="Malissen B">B. Malissen</name></author><author><name sortKey="Hasenkrug, K" uniqKey="Hasenkrug K">K. Hasenkrug</name></author><author><name sortKey="Kassiotis, G" uniqKey="Kassiotis G">G. Kassiotis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bayer, W" uniqKey="Bayer W">W. Bayer</name></author><author><name sortKey="Tenbusch, M" uniqKey="Tenbusch M">M. Tenbusch</name></author><author><name sortKey="Lietz, R" uniqKey="Lietz R">R. Lietz</name></author><author><name sortKey="Johrden, L" uniqKey="Johrden L">L. Johrden</name></author><author><name sortKey="Schimmer, S" uniqKey="Schimmer S">S. Schimmer</name></author><author><name sortKey="Uberla, K" uniqKey="Uberla K">K. Uberla</name></author><author><name sortKey="Dittmer, U" uniqKey="Dittmer U">U. Dittmer</name></author><author><name sortKey="Wildner, O" uniqKey="Wildner O">O. Wildner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brown, D M" uniqKey="Brown D">D.M. Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brown, D M" uniqKey="Brown D">D.M. Brown</name></author><author><name sortKey="Lampe, A T" uniqKey="Lampe A">A.T. Lampe</name></author><author><name sortKey="Workman, A M" uniqKey="Workman A">A.M. Workman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheroutre, H" uniqKey="Cheroutre H">H. Cheroutre</name></author><author><name sortKey="Husain, M M" uniqKey="Husain M">M.M. Husain</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, Y S" uniqKey="Choi Y">Y.S. Choi</name></author><author><name sortKey="Gullicksrud, J A" uniqKey="Gullicksrud J">J.A. Gullicksrud</name></author><author><name sortKey="Xing, S" uniqKey="Xing S">S. Xing</name></author><author><name sortKey="Zeng, Z" uniqKey="Zeng Z">Z. Zeng</name></author><author><name sortKey="Shan, Q" uniqKey="Shan Q">Q. Shan</name></author><author><name sortKey="Li, F" uniqKey="Li F">F. Li</name></author><author><name sortKey="Love, P E" uniqKey="Love P">P.E. Love</name></author><author><name sortKey="Peng, W" uniqKey="Peng W">W. Peng</name></author><author><name sortKey="Xue, H H" uniqKey="Xue H">H.H. Xue</name></author><author><name sortKey="Crotty, S" uniqKey="Crotty S">S. Crotty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crawford, A" uniqKey="Crawford A">A. Crawford</name></author><author><name sortKey="Angelosanto, J M" uniqKey="Angelosanto J">J.M. Angelosanto</name></author><author><name sortKey="Kao, C" uniqKey="Kao C">C. Kao</name></author><author><name sortKey="Doering, T A" uniqKey="Doering T">T.A. Doering</name></author><author><name sortKey="Odorizzi, P M" uniqKey="Odorizzi P">P.M. Odorizzi</name></author><author><name sortKey="Barnett, B E" uniqKey="Barnett B">B.E. Barnett</name></author><author><name sortKey="Wherry, E J" uniqKey="Wherry E">E.J. Wherry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crotty, S" uniqKey="Crotty S">S. Crotty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cullen, S P" uniqKey="Cullen S">S.P. Cullen</name></author><author><name sortKey="Brunet, M" uniqKey="Brunet M">M. Brunet</name></author><author><name sortKey="Martin, S J" uniqKey="Martin S">S.J. Martin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dittmer, U" uniqKey="Dittmer U">U. Dittmer</name></author><author><name sortKey="Brooks, D M" uniqKey="Brooks D">D.M. Brooks</name></author><author><name sortKey="Hasenkrug, K J" uniqKey="Hasenkrug K">K.J. Hasenkrug</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gong, D" uniqKey="Gong D">D. Gong</name></author><author><name sortKey="Malek, T R" uniqKey="Malek T">T.R. Malek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Han, S" uniqKey="Han S">S. Han</name></author><author><name sortKey="Asoyan, A" uniqKey="Asoyan A">A. Asoyan</name></author><author><name sortKey="Rabenstein, H" uniqKey="Rabenstein H">H. Rabenstein</name></author><author><name sortKey="Nakano, N" uniqKey="Nakano N">N. Nakano</name></author><author><name sortKey="Obst, R" uniqKey="Obst R">R. Obst</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hasenkrug, K J" uniqKey="Hasenkrug K">K.J. Hasenkrug</name></author><author><name sortKey="Chesebro, B" uniqKey="Chesebro B">B. Chesebro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hirschhorn Cymerman, D" uniqKey="Hirschhorn Cymerman D">D. Hirschhorn-Cymerman</name></author><author><name sortKey="Budhu, S" uniqKey="Budhu S">S. Budhu</name></author><author><name sortKey="Kitano, S" uniqKey="Kitano S">S. Kitano</name></author><author><name sortKey="Liu, C" uniqKey="Liu C">C. Liu</name></author><author><name sortKey="Zhao, F" uniqKey="Zhao F">F. Zhao</name></author><author><name sortKey="Zhong, H" uniqKey="Zhong H">H. Zhong</name></author><author><name sortKey="Lesokhin, A M" uniqKey="Lesokhin A">A.M. Lesokhin</name></author><author><name sortKey="Avogadri Connors, F" uniqKey="Avogadri Connors F">F. Avogadri-Connors</name></author><author><name sortKey="Yuan, J" uniqKey="Yuan J">J. Yuan</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hua, L" uniqKey="Hua L">L. Hua</name></author><author><name sortKey="Yao, S" uniqKey="Yao S">S. Yao</name></author><author><name sortKey="Pham, D" uniqKey="Pham D">D. Pham</name></author><author><name sortKey="Jiang, L" uniqKey="Jiang L">L. Jiang</name></author><author><name sortKey="Wright, J" uniqKey="Wright J">J. Wright</name></author><author><name sortKey="Sawant, D" uniqKey="Sawant D">D. Sawant</name></author><author><name sortKey="Dent, A L" uniqKey="Dent A">A.L. Dent</name></author><author><name sortKey="Braciale, T J" uniqKey="Braciale T">T.J. Braciale</name></author><author><name sortKey="Kaplan, M H" uniqKey="Kaplan M">M.H. Kaplan</name></author><author><name sortKey="Sun, J" uniqKey="Sun J">J. Sun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kaji, T" uniqKey="Kaji T">T. Kaji</name></author><author><name sortKey="Ishige, A" uniqKey="Ishige A">A. Ishige</name></author><author><name sortKey="Hikida, M" uniqKey="Hikida M">M. Hikida</name></author><author><name sortKey="Taka, J" uniqKey="Taka J">J. Taka</name></author><author><name sortKey="Hijikata, A" uniqKey="Hijikata A">A. Hijikata</name></author><author><name sortKey="Kubo, M" uniqKey="Kubo M">M. Kubo</name></author><author><name sortKey="Nagashima, T" uniqKey="Nagashima T">T. Nagashima</name></author><author><name sortKey="Takahashi, Y" uniqKey="Takahashi Y">Y. Takahashi</name></author><author><name sortKey="Kurosaki, T" uniqKey="Kurosaki T">T. Kurosaki</name></author><author><name sortKey="Okada, M" uniqKey="Okada M">M. Okada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kallies, A" uniqKey="Kallies A">A. Kallies</name></author><author><name sortKey="Xin, A" uniqKey="Xin A">A. Xin</name></author><author><name sortKey="Belz, G T" uniqKey="Belz G">G.T. Belz</name></author><author><name sortKey="Nutt, S L" uniqKey="Nutt S">S.L. Nutt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kitamura, D" uniqKey="Kitamura D">D. Kitamura</name></author><author><name sortKey="Roes, J" uniqKey="Roes J">J. Roes</name></author><author><name sortKey="Kuhn, R" uniqKey="Kuhn R">R. Kühn</name></author><author><name sortKey="Rajewsky, K" uniqKey="Rajewsky K">K. Rajewsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klarnet, J P" uniqKey="Klarnet J">J.P. Klarnet</name></author><author><name sortKey="Kern, D E" uniqKey="Kern D">D.E. Kern</name></author><author><name sortKey="Okuno, K" uniqKey="Okuno K">K. Okuno</name></author><author><name sortKey="Holt, C" uniqKey="Holt C">C. Holt</name></author><author><name sortKey="Lilly, F" uniqKey="Lilly F">F. Lilly</name></author><author><name sortKey="Greenberg, P D" uniqKey="Greenberg P">P.D. Greenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klinger, M" uniqKey="Klinger M">M. Klinger</name></author><author><name sortKey="Kim, J K" uniqKey="Kim J">J.K. Kim</name></author><author><name sortKey="Chmura, S A" uniqKey="Chmura S">S.A. Chmura</name></author><author><name sortKey="Barczak, A" uniqKey="Barczak A">A. Barczak</name></author><author><name sortKey="Erle, D J" uniqKey="Erle D">D.J. Erle</name></author><author><name sortKey="Killeen, N" uniqKey="Killeen N">N. Killeen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Manzke, N" uniqKey="Manzke N">N. Manzke</name></author><author><name sortKey="Akhmetzyanova, I" uniqKey="Akhmetzyanova I">I. Akhmetzyanova</name></author><author><name sortKey="Hasenkrug, K J" uniqKey="Hasenkrug K">K.J. Hasenkrug</name></author><author><name sortKey="Trilling, M" uniqKey="Trilling M">M. Trilling</name></author><author><name sortKey="Zelinskyy, G" uniqKey="Zelinskyy G">G. Zelinskyy</name></author><author><name sortKey="Dittmer, U" uniqKey="Dittmer U">U. Dittmer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marques, R" uniqKey="Marques R">R. Marques</name></author><author><name sortKey="Williams, A" uniqKey="Williams A">A. Williams</name></author><author><name sortKey="Eksmond, U" uniqKey="Eksmond U">U. Eksmond</name></author><author><name sortKey="Wullaert, A" uniqKey="Wullaert A">A. Wullaert</name></author><author><name sortKey="Killeen, N" uniqKey="Killeen N">N. Killeen</name></author><author><name sortKey="Pasparakis, M" uniqKey="Pasparakis M">M. Pasparakis</name></author><author><name sortKey="Kioussis, D" uniqKey="Kioussis D">D. Kioussis</name></author><author><name sortKey="Kassiotis, G" uniqKey="Kassiotis G">G. Kassiotis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Merkenschlager, J" uniqKey="Merkenschlager J">J. Merkenschlager</name></author><author><name sortKey="Ploquin, M J" uniqKey="Ploquin M">M.J. Ploquin</name></author><author><name sortKey="Eksmond, U" uniqKey="Eksmond U">U. Eksmond</name></author><author><name sortKey="Andargachew, R" uniqKey="Andargachew R">R. Andargachew</name></author><author><name sortKey="Thorborn, G" uniqKey="Thorborn G">G. Thorborn</name></author><author><name sortKey="Filby, A" uniqKey="Filby A">A. Filby</name></author><author><name sortKey="Pepper, M" uniqKey="Pepper M">M. Pepper</name></author><author><name sortKey="Evavold, B" uniqKey="Evavold B">B. Evavold</name></author><author><name sortKey="Kassiotis, G" uniqKey="Kassiotis G">G. Kassiotis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mombaerts, P" uniqKey="Mombaerts P">P. Mombaerts</name></author><author><name sortKey="Iacomini, J" uniqKey="Iacomini J">J. Iacomini</name></author><author><name sortKey="Johnson, R S" uniqKey="Johnson R">R.S. Johnson</name></author><author><name sortKey="Herrup, K" uniqKey="Herrup K">K. Herrup</name></author><author><name sortKey="Tonegawa, S" uniqKey="Tonegawa S">S. Tonegawa</name></author><author><name sortKey="Papaioannou, V E" uniqKey="Papaioannou V">V.E. Papaioannou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mouchacca, P" uniqKey="Mouchacca P">P. Mouchacca</name></author><author><name sortKey="Schmitt Verhulst, A M" uniqKey="Schmitt Verhulst A">A.M. Schmitt-Verhulst</name></author><author><name sortKey="Boyer, C" uniqKey="Boyer C">C. Boyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mucida, D" uniqKey="Mucida D">D. Mucida</name></author><author><name sortKey="Husain, M M" uniqKey="Husain M">M.M. Husain</name></author><author><name sortKey="Muroi, S" uniqKey="Muroi S">S. Muroi</name></author><author><name sortKey="Van Wijk, F" uniqKey="Van Wijk F">F. van Wijk</name></author><author><name sortKey="Shinnakasu, R" uniqKey="Shinnakasu R">R. Shinnakasu</name></author><author><name sortKey="Naoe, Y" uniqKey="Naoe Y">Y. Naoe</name></author><author><name sortKey="Reis, B S" uniqKey="Reis B">B.S. Reis</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y. Huang</name></author><author><name sortKey="Lambolez, F" uniqKey="Lambolez F">F. Lambolez</name></author><author><name sortKey="Docherty, M" uniqKey="Docherty M">M. Docherty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Hea, J J" uniqKey="O Hea J">J.J. O’Shea</name></author><author><name sortKey="Paul, W E" uniqKey="Paul W">W.E. Paul</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pike, R" uniqKey="Pike R">R. Pike</name></author><author><name sortKey="Filby, A" uniqKey="Filby A">A. Filby</name></author><author><name sortKey="Ploquin, M J" uniqKey="Ploquin M">M.J. Ploquin</name></author><author><name sortKey="Eksmond, U" uniqKey="Eksmond U">U. Eksmond</name></author><author><name sortKey="Marques, R" uniqKey="Marques R">R. Marques</name></author><author><name sortKey="Antunes, I" uniqKey="Antunes I">I. Antunes</name></author><author><name sortKey="Hasenkrug, K" uniqKey="Hasenkrug K">K. Hasenkrug</name></author><author><name sortKey="Kassiotis, G" uniqKey="Kassiotis G">G. Kassiotis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ploquin, M J" uniqKey="Ploquin M">M.J. Ploquin</name></author><author><name sortKey="Eksmond, U" uniqKey="Eksmond U">U. Eksmond</name></author><author><name sortKey="Kassiotis, G" uniqKey="Kassiotis G">G. Kassiotis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qin, Z" uniqKey="Qin Z">Z. Qin</name></author><author><name sortKey="Richter, G" uniqKey="Richter G">G. Richter</name></author><author><name sortKey="Schuler, T" uniqKey="Schuler T">T. Schüler</name></author><author><name sortKey="Ibe, S" uniqKey="Ibe S">S. Ibe</name></author><author><name sortKey="Cao, X" uniqKey="Cao X">X. Cao</name></author><author><name sortKey="Blankenstein, T" uniqKey="Blankenstein T">T. Blankenstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qui, H Z" uniqKey="Qui H">H.Z. Qui</name></author><author><name sortKey="Hagymasi, A T" uniqKey="Hagymasi A">A.T. Hagymasi</name></author><author><name sortKey="Bandyopadhyay, S" uniqKey="Bandyopadhyay S">S. Bandyopadhyay</name></author><author><name sortKey="St Rose, M C" uniqKey="St Rose M">M.C. St. Rose</name></author><author><name sortKey="Ramanarasimhaiah, R" uniqKey="Ramanarasimhaiah R">R. Ramanarasimhaiah</name></author><author><name sortKey="Menoret, A" uniqKey="Menoret A">A. Ménoret</name></author><author><name sortKey="Mittler, R S" uniqKey="Mittler R">R.S. Mittler</name></author><author><name sortKey="Gordon, S M" uniqKey="Gordon S">S.M. Gordon</name></author><author><name sortKey="Reiner, S L" uniqKey="Reiner S">S.L. Reiner</name></author><author><name sortKey="Vella, A T" uniqKey="Vella A">A.T. Vella</name></author><author><name sortKey="Adler, A J" uniqKey="Adler A">A.J. Adler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reis, B S" uniqKey="Reis B">B.S. Reis</name></author><author><name sortKey="Rogoz, A" uniqKey="Rogoz A">A. Rogoz</name></author><author><name sortKey="Costa Pinto, F A" uniqKey="Costa Pinto F">F.A. Costa-Pinto</name></author><author><name sortKey="Taniuchi, I" uniqKey="Taniuchi I">I. Taniuchi</name></author><author><name sortKey="Mucida, D" uniqKey="Mucida D">D. Mucida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Soghoian, D Z" uniqKey="Soghoian D">D.Z. Soghoian</name></author><author><name sortKey="Streeck, H" uniqKey="Streeck H">H. Streeck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Srinivas, S" uniqKey="Srinivas S">S. Srinivas</name></author><author><name sortKey="Watanabe, T" uniqKey="Watanabe T">T. Watanabe</name></author><author><name sortKey="Lin, C S" uniqKey="Lin C">C.S. Lin</name></author><author><name sortKey="William, C M" uniqKey="William C">C.M. William</name></author><author><name sortKey="Tanabe, Y" uniqKey="Tanabe Y">Y. Tanabe</name></author><author><name sortKey="Jessell, T M" uniqKey="Jessell T">T.M. Jessell</name></author><author><name sortKey="Costantini, F" uniqKey="Costantini F">F. Costantini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Swain, S L" uniqKey="Swain S">S.L. Swain</name></author><author><name sortKey="Mckinstry, K K" uniqKey="Mckinstry K">K.K. McKinstry</name></author><author><name sortKey="Strutt, T M" uniqKey="Strutt T">T.M. Strutt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takeuchi, A" uniqKey="Takeuchi A">A. Takeuchi</name></author><author><name sortKey="Badr Mel, S" uniqKey="Badr Mel S">S. Badr Mel</name></author><author><name sortKey="Miyauchi, K" uniqKey="Miyauchi K">K. Miyauchi</name></author><author><name sortKey="Ishihara, C" uniqKey="Ishihara C">C. Ishihara</name></author><author><name sortKey="Onishi, R" uniqKey="Onishi R">R. Onishi</name></author><author><name sortKey="Guo, Z" uniqKey="Guo Z">Z. Guo</name></author><author><name sortKey="Sasaki, Y" uniqKey="Sasaki Y">Y. Sasaki</name></author><author><name sortKey="Ike, H" uniqKey="Ike H">H. Ike</name></author><author><name sortKey="Takumi, A" uniqKey="Takumi A">A. Takumi</name></author><author><name sortKey="Tsuji, N M" uniqKey="Tsuji N">N.M. Tsuji</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thorborn, G" uniqKey="Thorborn G">G. Thorborn</name></author><author><name sortKey="Ploquin, M J" uniqKey="Ploquin M">M.J. Ploquin</name></author><author><name sortKey="Eksmond, U" uniqKey="Eksmond U">U. Eksmond</name></author><author><name sortKey="Pike, R" uniqKey="Pike R">R. Pike</name></author><author><name sortKey="Bayer, W" uniqKey="Bayer W">W. Bayer</name></author><author><name sortKey="Dittmer, U" uniqKey="Dittmer U">U. Dittmer</name></author><author><name sortKey="Hasenkrug, K J" uniqKey="Hasenkrug K">K.J. Hasenkrug</name></author><author><name sortKey="Pepper, M" uniqKey="Pepper M">M. Pepper</name></author><author><name sortKey="Kassiotis, G" uniqKey="Kassiotis G">G. Kassiotis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tsuji Kawahara, S" uniqKey="Tsuji Kawahara S">S. Tsuji-Kawahara</name></author><author><name sortKey="Kawabata, H" uniqKey="Kawabata H">H. Kawabata</name></author><author><name sortKey="Matsukuma, H" uniqKey="Matsukuma H">H. Matsukuma</name></author><author><name sortKey="Kinoshita, S" uniqKey="Kinoshita S">S. Kinoshita</name></author><author><name sortKey="Chikaishi, T" uniqKey="Chikaishi T">T. Chikaishi</name></author><author><name sortKey="Sakamoto, M" uniqKey="Sakamoto M">M. Sakamoto</name></author><author><name sortKey="Kawasaki, Y" uniqKey="Kawasaki Y">Y. Kawasaki</name></author><author><name sortKey="Miyazawa, M" uniqKey="Miyazawa M">M. Miyazawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van De Berg, P J" uniqKey="Van De Berg P">P.J. van de Berg</name></author><author><name sortKey="Van Leeuwen, E M" uniqKey="Van Leeuwen E">E.M. van Leeuwen</name></author><author><name sortKey="Ten Berge, I J" uniqKey="Ten Berge I">I.J. ten Berge</name></author><author><name sortKey="Van Lier, R" uniqKey="Van Lier R">R. van Lier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vinuesa, C G" uniqKey="Vinuesa C">C.G. Vinuesa</name></author><author><name sortKey="Linterman, M A" uniqKey="Linterman M">M.A. Linterman</name></author><author><name sortKey="Yu, D" uniqKey="Yu D">D. Yu</name></author><author><name sortKey="Maclennan, I C" uniqKey="Maclennan I">I.C. MacLennan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, T" uniqKey="Wu T">T. Wu</name></author><author><name sortKey="Shin, H M" uniqKey="Shin H">H.M. Shin</name></author><author><name sortKey="Moseman, E A" uniqKey="Moseman E">E.A. Moseman</name></author><author><name sortKey="Ji, Y" uniqKey="Ji Y">Y. Ji</name></author><author><name sortKey="Huang, B" uniqKey="Huang B">B. Huang</name></author><author><name sortKey="Harly, C" uniqKey="Harly C">C. Harly</name></author><author><name sortKey="Sen, J M" uniqKey="Sen J">J.M. Sen</name></author><author><name sortKey="Berg, L J" uniqKey="Berg L">L.J. Berg</name></author><author><name sortKey="Gattinoni, L" uniqKey="Gattinoni L">L. Gattinoni</name></author><author><name sortKey="Mcgavern, D B" uniqKey="Mcgavern D">D.B. McGavern</name></author><author><name sortKey="Schwartzberg, P L" uniqKey="Schwartzberg P">P.L. Schwartzberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, L" uniqKey="Xu L">L. Xu</name></author><author><name sortKey="Cao, Y" uniqKey="Cao Y">Y. Cao</name></author><author><name sortKey="Xie, Z" uniqKey="Xie Z">Z. Xie</name></author><author><name sortKey="Huang, Q" uniqKey="Huang Q">Q. Huang</name></author><author><name sortKey="Bai, Q" uniqKey="Bai Q">Q. Bai</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X. Yang</name></author><author><name sortKey="He, R" uniqKey="He R">R. He</name></author><author><name sortKey="Hao, Y" uniqKey="Hao Y">Y. Hao</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H. Wang</name></author><author><name sortKey="Zhao, T" uniqKey="Zhao T">T. Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Young, G R" uniqKey="Young G">G.R. Young</name></author><author><name sortKey="Ploquin, M J" uniqKey="Ploquin M">M.J. Ploquin</name></author><author><name sortKey="Eksmond, U" uniqKey="Eksmond U">U. Eksmond</name></author><author><name sortKey="Wadwa, M" uniqKey="Wadwa M">M. Wadwa</name></author><author><name sortKey="Stoye, J P" uniqKey="Stoye J">J.P. Stoye</name></author><author><name sortKey="Kassiotis, G" uniqKey="Kassiotis G">G. Kassiotis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, J" uniqKey="Zhu J">J. Zhu</name></author><author><name sortKey="Yamane, H" uniqKey="Yamane H">H. Yamane</name></author><author><name sortKey="Paul, W E" uniqKey="Paul W">W.E. Paul</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Cell Rep</journal-id><journal-id journal-id-type="iso-abbrev">Cell Rep</journal-id><journal-title-group><journal-title>Cell Reports</journal-title></journal-title-group><issn pub-type="epub">2211-1247</issn><publisher><publisher-name>Cell Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27806296</article-id><article-id pub-id-type="pmc">5149578</article-id><article-id pub-id-type="publisher-id">S2211-1247(16)31399-7</article-id><article-id pub-id-type="doi">10.1016/j.celrep.2016.10.013</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Donnarumma</surname><given-names>Tiziano</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Young</surname><given-names>George R.</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff2" ref-type="aff">2</xref></contrib><contrib contrib-type="author"><name><surname>Merkenschlager</surname><given-names>Julia</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Eksmond</surname><given-names>Urszula</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Bongard</surname><given-names>Nadine</given-names></name><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Nutt</surname><given-names>Stephen L.</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Boyer</surname><given-names>Claude</given-names></name><xref rid="aff6" ref-type="aff">6</xref></contrib><contrib contrib-type="author"><name><surname>Dittmer</surname><given-names>Ulf</given-names></name><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Le-Trilling</surname><given-names>Vu Thuy Khanh</given-names></name><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Trilling</surname><given-names>Mirko</given-names></name><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Bayer</surname><given-names>Wibke</given-names></name><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Kassiotis</surname><given-names>George</given-names></name><email>george.kassiotis@crick.ac.uk</email><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff3" ref-type="aff">3</xref><xref rid="fn1" ref-type="fn">7</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK</aff><aff id="aff2"><label>2</label>Retrovirus-Host Interactions, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK</aff><aff id="aff3"><label>3</label>Department of Medicine, Faculty of Medicine, Imperial College London, London W2 1PG, UK</aff><aff id="aff4"><label>4</label>Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany</aff><aff id="aff5"><label>5</label>The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia</aff><aff id="aff6"><label>6</label>Centre d’Immunologie de Marseille-Luminy (CIML), Aix-Marseille University, UM2, Marseille 13288, France</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author <email>george.kassiotis@crick.ac.uk</email></corresp><fn id="fn1"><label>7</label><p id="ntpara0010">Lead Contact</p></fn></author-notes><pub-date pub-type="pmc-release"><day>01</day><month>11</month><year>2016</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="collection"><day>01</day><month>11</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>01</day><month>11</month><year>2016</year></pub-date><volume>17</volume><issue>6</issue><fpage>1571</fpage><lpage>1583</lpage><history><date date-type="received"><day>7</day><month>6</month><year>2016</year></date><date date-type="rev-recd"><day>31</day><month>8</month><year>2016</year></date><date date-type="accepted"><day>4</day><month>10</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 The Author(s)</copyright-statement><copyright-year>2016</copyright-year><license license-type="CC BY" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</license-p></license></permissions><abstract id="abs0010"><title>Summary</title><p>CD4<sup>+</sup> T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8<sup>+</sup> T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4<sup>+</sup> T cells. However, the conditions that induce CD4<sup>+</sup> CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)<sup>+</sup> CD4<sup>+</sup> CTLs, which distinguishes them from other CD4<sup>+</sup> T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature. The balance between CD4<sup>+</sup> CTL and Tfh differentiation heavily depends on the class of infecting virus and is jointly regulated by the Tfh-related transcription factors <italic>Bcl6</italic> and <italic>Tcf7</italic> (encoding TCF-1) and by the expression of the inhibitory receptors PD-1 and LAG3. This unique profile of CD4<sup>+</sup> CTLs offers targets for their study, and its antagonism by the Tfh program separates CD4<sup>+</sup> T cells with either helper or killer functions.</p></abstract><abstract abstract-type="graphical" id="abs0015"><title>Graphical Abstract</title><fig id="undfig1" position="anchor"><graphic xlink:href="fx1"></graphic></fig></abstract><abstract abstract-type="author-highlights" id="abs0020"><title>Highlights</title><p><list list-type="simple"><list-item id="u0010"><label>•</label><p>Adenoviruses prime CD4 T cells with CTL potential, but retroviruses do not</p></list-item><list-item id="u0015"><label>•</label><p>CD4 CTLs are transcriptionally distinguishable from other Th cells</p></list-item><list-item id="u0020"><label>•</label><p>The CD4 CTL program is the direct opposite of the Tfh program</p></list-item><list-item id="u0025"><label>•</label><p>CD4 CTLs are restrained by the TCF-1-Bcl6 nexus and by PD-1 and LAG3</p></list-item></list></p></abstract><abstract abstract-type="teaser" id="abs0025"><p>“Helper” CD4 T cells can also exhibit granzyme-mediated cytotoxicity. Donnarumma et al. investigate the conditions that induce CD4 CTLs and describe the dominant effect of the class of infecting virus. They uncover a unique transcriptional signature of CD4 CTLs and its multi-layered control.</p></abstract><kwd-group id="kwrds0010"><title>Keywords</title><kwd>cytotoxic CD4 T cells</kwd><kwd>retroviral infection</kwd><kwd>adenovirus-based vaccination</kwd><kwd>single-cell RNA sequencing</kwd><kwd>inhibitory receptors</kwd><kwd>CD4 T cell differentiation</kwd><kwd>antiviral immunity</kwd></kwd-group></article-meta><notes><p id="misc0010">Published: November 1, 2016</p></notes></front><floats-group><fig id="fig1"><label>Figure 1</label><caption><p>CD4<sup>+</sup> CTL Development Depends on Infecting Virus</p><p>(A) Expression of <italic>Gzmb</italic>, relative to <italic>Hprt</italic>, assessed by qRT-PCR in env-reactive donor EF4.1 CD4<sup>+</sup> T cells purified from the spleens of recipient mice, 7 days after adoptive transfer and FV infection or Ad5.pIX-gp70 immunization. Plotted are the mean values (±SEM) of four technical replicates, from two experiments with five mice per group per experiment.</p><p>(B) Flow-cytometric detection (left) and efficiency of in vivo killing (right) of env<sub>122–141</sub>-pulsed CD45.1<sup>+</sup> and non-pulsed CD45.2<sup>+</sup> B cells in host splenocytes, 24 hr after transfer into CD45.1<sup>+</sup>CD45.2<sup>+</sup> hosts (5 × 10<sup>6</sup> of each per host) that had also received EF4.1 CD4<sup>+</sup> T cells and had either been infected with FV or immunized with Ad5.pIX-gp70 7 days earlier.</p><p>(C) Flow-cytometric detection (left) and efficiency of in vitro killing (right) of env<sub>122–141</sub>-pulsed and non-pulsed B cells, 2 hr after culture with env-reactive donor EF4.1 CD4<sup>+</sup> T cells purified from the spleens of recipient mice, 7 days after adoptive transfer and FV infection or Ad5.pIX-gp70 immunization.</p><p>(D) Flow-cytometric detection of intracellular GzmB host naive (CD44<sup>−</sup>) or env-reactive (CD44<sup>+</sup>) donor EF4.1 CD4<sup>+</sup> T cells (left) and frequency of GzmB<sup>+</sup> cells in env-reactive donor EF4.1 CD4<sup>+</sup> T cells (right) in the spleens of recipient mice, 7 days after adoptive transfer and FV infection or Ad5.pIX-gp70 immunization.</p><p>(E) Frequency of intracellular GzmB<sup>+</sup> cells in env-reactive donor EF4.1 CD4<sup>+</sup> T cells in the spleens of recipient mice, 7 days after adoptive transfer and FV infection, F-MLV-N infection, env<sub>122–141</sub> peptide immunization in the Sigma Adjuvant System, FBL-3 leukemia cell transplantation, mCMV.env infection, or Ad5.pIX-gp70 immunization.</p><p>In (B) to (E), each symbol in the scatterplots represents an individual recipient mouse.</p><p>See also <xref rid="mmc1" ref-type="supplementary-material">Figures S1</xref>, <xref rid="mmc1" ref-type="supplementary-material">S2</xref>, and <xref rid="mmc1" ref-type="supplementary-material">S3</xref>.</p></caption><graphic xlink:href="gr1"></graphic></fig><fig id="fig2"><label>Figure 2</label><caption><p>Antagonistic CD4<sup>+</sup> CTL and Tfh Development</p><p>(A) <italic>Cd4</italic> and <italic>Gzmb</italic> expression, assessed by single-cell RNA sequencing, in env-reactive donor EF4.1 CD4<sup>+</sup> T cells purified from the spleens of recipient mice, 7 days after adoptive transfer and FV infection or Ad5.pIX-gp70 immunization. Each symbol shows the log<sub>2</sub>-transformed normalized reads from an individual cell from one of two experiments. Numbers within the plots denote the number of cells positive for expression of the indicated gene.</p><p>(B) <italic>Tcf7</italic> and <italic>Bcl6</italic> expression in the same cells as in (A).</p><p>(C) Expression of <italic>Tcf7</italic> and <italic>Bcl6</italic>, relative to <italic>Hprt</italic>, assessed by qRT-PCR in bulk env-reactive donor EF4.1 CD4<sup>+</sup> T cells purified from the spleens of recipient mice, 7 days after adoptive transfer and FV infection or Ad5.pIX-gp70 immunization. Plotted are the mean values (±SEM) of four technical replicates from two experiments with four mice per group per experiment.</p><p>(D) Heatmap of gene expression, assessed by single-cell RNA sequencing, comparing <italic>Gzmb</italic><sup><italic>+</italic></sup> and <italic>Gzmb</italic><sup>−</sup> subsets in env-reactive donor EF4.1 CD4<sup>+</sup> T cells purified from the spleens of recipient mice, 7 days after adoptive transfer and priming. CD4<sup>+</sup> T cells from both FV infection and Ad5.pIX-gp70 immunization are included. A select set of genes from the complete list in <xref rid="mmc2" ref-type="supplementary-material">Table S1</xref> is shown.</p><p>(E) Flow-cytometric correlation of intracellular GzmB and surface markers CXCR6, CD39, CD150, and CD226 (left) and frequency of surface marker<sup>+</sup> cells separately in GzmB<sup>−</sup> and GzmB<sup>+</sup> cells within env-reactive (CD44<sup>+</sup>) donor EF4.1 CD4<sup>+</sup> T cells (right) in the spleens of recipient mice, 7 days after adoptive transfer and Ad5.pIX-gp70 immunization. In the scatterplots, each symbol represents an individual recipient.</p><p>(F) Expression of <italic>Prdm1</italic>, <italic>Bcl6</italic>, <italic>Lef1</italic>, <italic>Tcf7</italic>, <italic>Zbtb7b</italic>, and <italic>Runx3</italic> assessed by single-cell RNA sequencing, separately in <italic>Gzmb</italic><sup><italic>+</italic></sup> and <italic>Gzmb</italic><sup><italic>−</italic></sup> env-reactive donor EF4.1 CD4<sup>+</sup> T cells purified from the spleens of recipient mice, 7 days after adoptive transfer and Ad5.pIX-gp70 immunization.</p><p>See also <xref rid="mmc1" ref-type="supplementary-material">Figures S4</xref>, <xref rid="mmc1" ref-type="supplementary-material">S5</xref>, and <xref rid="mmc1" ref-type="supplementary-material">S6</xref> and <xref rid="mmc2" ref-type="supplementary-material">Table S1</xref>.</p></caption><graphic xlink:href="gr2"></graphic></fig><fig id="fig3"><label>Figure 3</label><caption><p>Bcl6 Suppresses CD4<sup>+</sup> CTL Development at the Population Level</p><p>(A) Delineation of env-reactive donor EF4.1 CD4<sup>+</sup> T cells according to YFP expression. Histograms show gated env-reactive EF4.1 CD4<sup>+</sup> T cells from <italic>Bcl6</italic><sup>wt</sup> or <italic>Bcl6</italic><sup>fl</sup> donors, found in the spleens of recipient mice, 7 days after adoptive transfer and FV infection or Ad5.pIX-gp70 immunization. YFP expression reports activation of the <italic>Tnfrsf4</italic> gene and, in the case of <italic>Bcl6</italic><sup>fl</sup> donor CD4<sup>+</sup> T cells, also loss of <italic>Bcl6</italic>. Numbers within the plots denote the proportion of YFP<sup>+</sup> cells.</p><p>(B) Expression of the indicated gene, relative to <italic>Hprt</italic>, assessed by qRT-PCR in the respective bulk subset of env-reactive donor EF4.1 CD4<sup>+</sup> T cells shown immediately above in (A). Plotted are the mean values (±SEM) of two technical replicates, from two experiments with five mice per group per experiment.</p><p>See also <xref rid="mmc1" ref-type="supplementary-material">Figures S7</xref>, <xref rid="mmc1" ref-type="supplementary-material">S8</xref>, and <xref rid="mmc1" ref-type="supplementary-material">S9</xref>.</p></caption><graphic xlink:href="gr3"></graphic></fig><fig id="fig4"><label>Figure 4</label><caption><p>Bcl6 Suppresses CD4<sup>+</sup> CTL Development at the Single-Cell Level</p><p>(A) Frequency of intracellular GzmB<sup>+</sup> cells in bulk <italic>Bcl6</italic><sup>wt</sup> or <italic>Bcl6</italic><sup>fl</sup> env-reactive donor EF4.1 CD4<sup>+</sup> T cells in the spleens of recipient mice, 7 days after adoptive transfer and FV infection or Ad5.pIX-gp70 immunization. Each symbol represents an individual mouse from one representative of two experiments.</p><p>(B) <italic>Cd4</italic> and <italic>Gzmb</italic> expression, assessed by single-cell RNA sequencing, in YFP<sup>+</sup><italic>Bcl6</italic><sup>fl</sup> env-reactive donor EF4.1 CD4<sup>+</sup> T cells purified from the spleens of recipient mice, 7 days after adoptive transfer and FV infection or Ad5.pIX-gp70 immunization.</p><p>(C) <italic>Il21</italic>, <italic>Il10</italic>, and <italic>Ifng</italic> expression, assessed by single-cell RNA sequencing, in YFP<sup>+</sup><italic>Bcl6</italic><sup>wt</sup>, and <italic>Bcl6</italic><sup>fl</sup> env-reactive donor EF4.1 CD4<sup>+</sup> T cells purified from the spleens of recipient mice, 7 days after adoptive transfer and FV infection or Ad5.pIX-gp70 immunization.</p></caption><graphic xlink:href="gr4"></graphic></fig><fig id="fig5"><label>Figure 5</label><caption><p>CD4<sup>+</sup> CTL and Th1 Cells Are Transcriptionally Distinct</p><p>(A) <italic>Gzmb</italic> and <italic>Ifng</italic> expression, assessed by single-cell RNA sequencing, in env-reactive donor EF4.1 CD4<sup>+</sup> T cells purified from the spleens of recipient mice, 7 days after adoptive transfer and priming. Both <italic>Bcl6</italic><sup>wt</sup> and <italic>Bcl6</italic><sup>fl</sup> CD4<sup>+</sup> T cells from both FV infection and Ad5.pIX-gp70 immunization are included.</p><p>(B) Flow-cytometric detection of intracellular GzmB and IFN-γ in host naive (CD44<sup>−</sup>) or env-reactive (CD44<sup>+</sup>) donor EF4.1 CD4<sup>+</sup> T cells in the spleens of recipient mice, 7 days after adoptive transfer and Ad5.pIX-gp70 immunization. The plot is representative of four recipients.</p><p>(C) Flow-cytometric correlation of intracellular GzmB and surface CD150 expression (left) and frequency of CD150<sup>+</sup> cells separately in GzmB<sup>−</sup> and GzmB<sup>+</sup> cells within IFN-γ<sup>+</sup> env-reactive (CD44<sup>+</sup>) donor EF4.1 CD4<sup>+</sup> T cells (right) in the spleens of recipient mice, 7 days after adoptive transfer and Ad5.pIX-gp70 immunization. In the scatterplot, each symbol represents an individual recipient.</p><p>(D) Heatmap of significantly (p = 3.95 × 10<sup>−4</sup>) regulated gene expression, assessed by single-cell RNA sequencing, comparing <italic>Ifng</italic><sup><italic>+</italic></sup><italic>Gzmb</italic><sup>+</sup> and <italic>Ifng</italic><sup><italic>+</italic></sup><italic>Gzmb</italic><sup>−</sup> subsets in the same cells as in (A).</p><p>(E) <italic>Prdm1</italic> and <italic>Tcf7</italic> expression, assessed by single-cell RNA sequencing, in the same cells as in (A).</p><p>(F) Flow-cytometric detection of Blimp1-GFP and CD44 expression in host and env-reactive donor CD4<sup>+</sup> T cells in the spleens of recipient mice, 7 days after adoptive transfer and Ad5.pIX-gp70 immunization.</p><p>(G) Expression of <italic>Prdm1</italic>, <italic>Tcf7</italic>, and <italic>Gzmb</italic>, relative to <italic>Hprt</italic>, assessed by qRT-PCR in bulk Blimp1-GFP<sup>+</sup> and Blimp1-GFP<sup>-</sup> subsets in env-reactive donor EF4.1 CD4<sup>+</sup> T cells purified from the spleens of recipient mice, 7 days after adoptive transfer and Ad5.pIX-gp70 immunization. Plotted are the mean values (±SEM) of two technical replicates from one experiment with five mice per group.</p><p>See also <xref rid="mmc1" ref-type="supplementary-material">Figures S10</xref> and <xref rid="mmc1" ref-type="supplementary-material">S11</xref>.</p></caption><graphic xlink:href="gr5"></graphic></fig><fig id="fig6"><label>Figure 6</label><caption><p>Layered Checkpoints in CD4<sup>+</sup> CTL Development</p><p>(A) <italic>Pcdc1</italic>, <italic>Lag3</italic>, <italic>Ctla4</italic>, and <italic>Havcr2</italic> expression, assessed by single-cell RNA sequencing, in env-reactive donor EF4.1 CD4<sup>+</sup> T cells purified from the spleens of recipient mice, 7 days after adoptive transfer and FV infection or Ad5.pIX-gp70 immunization. Both <italic>Bcl6</italic><sup>wt</sup> and <italic>Bcl6</italic><sup>fl</sup> CD4<sup>+</sup> T cells are included.</p><p>(B) Flow-cytometric detection of PD-1 and LAG3 expression in host naive (CD44<sup>−</sup>) and env-reactive (CD44<sup>+</sup>) donor CD4<sup>+</sup> T cells in the spleens of recipient mice, 7 days after adoptive transfer and FV infection or Ad5.pIX-gp70 immunization. Numbers within the plots denote the proportion of PD-1<sup>+</sup> and LAG3<sup>+</sup> cells in env-reactive donor CD4<sup>+</sup> T cells only.</p><p>(C) Median fluorescence intensity (MFI) of PD-1 and LAG3 staining in the same cells as in (B). Each symbol represents an individual recipient. The dashed line represents the MFI of PD-1 and LAG3 staining in host naive CD4<sup>+</sup> T cells.</p><p>(D) Frequency of intracellular GzmB<sup>+</sup> cells in bulk <italic>Bcl6</italic><sup>wt</sup> and <italic>Bcl6</italic><sup>fl</sup> env-reactive donor EF4.1 CD4<sup>+</sup> T cells in the spleens of either WT or B cell-deficient <italic>Ighm</italic><sup>−/−</sup> recipient mice, 7 days after adoptive transfer and FV infection. The indicated groups additionally received treatment with PD-1- and LAG3-blocking antibodies. Each symbol represents an individual recipient.</p><p>See also <xref rid="mmc1" ref-type="supplementary-material">Figures S12</xref>, <xref rid="mmc1" ref-type="supplementary-material">S13</xref>, <xref rid="mmc1" ref-type="supplementary-material">S14</xref>, and <xref rid="mmc1" ref-type="supplementary-material">S15</xref>.</p></caption><graphic xlink:href="gr6"></graphic></fig></floats-group></pmc><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>Royaume-Uni</li></country><region><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Marseille</li></settlement></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Donnarumma, Tiziano" sort="Donnarumma, Tiziano" uniqKey="Donnarumma T" first="Tiziano" last="Donnarumma">Tiziano Donnarumma</name></noRegion><name sortKey="Eksmond, Urszula" sort="Eksmond, Urszula" uniqKey="Eksmond U" first="Urszula" last="Eksmond">Urszula Eksmond</name><name sortKey="Kassiotis, George" sort="Kassiotis, George" uniqKey="Kassiotis G" first="George" last="Kassiotis">George Kassiotis</name><name sortKey="Kassiotis, George" sort="Kassiotis, George" uniqKey="Kassiotis G" first="George" last="Kassiotis">George Kassiotis</name><name sortKey="Merkenschlager, Julia" sort="Merkenschlager, Julia" uniqKey="Merkenschlager J" first="Julia" last="Merkenschlager">Julia Merkenschlager</name><name sortKey="Young, George R" sort="Young, George R" uniqKey="Young G" first="George R." last="Young">George R. Young</name><name sortKey="Young, George R" sort="Young, George R" uniqKey="Young G" first="George R." last="Young">George R. Young</name></country><country name="Allemagne"><noRegion><name sortKey="Bongard, Nadine" sort="Bongard, Nadine" uniqKey="Bongard N" first="Nadine" last="Bongard">Nadine Bongard</name></noRegion><name sortKey="Bayer, Wibke" sort="Bayer, Wibke" uniqKey="Bayer W" first="Wibke" last="Bayer">Wibke Bayer</name><name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name><name sortKey="Le Trilling, Vu Thuy Khanh" sort="Le Trilling, Vu Thuy Khanh" uniqKey="Le Trilling V" first="Vu Thuy Khanh" last="Le-Trilling">Vu Thuy Khanh Le-Trilling</name><name sortKey="Trilling, Mirko" sort="Trilling, Mirko" uniqKey="Trilling M" first="Mirko" last="Trilling">Mirko Trilling</name></country><country name="Australie"><noRegion><name sortKey="Nutt, Stephen L" sort="Nutt, Stephen L" uniqKey="Nutt S" first="Stephen L." last="Nutt">Stephen L. Nutt</name></noRegion></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Boyer, Claude" sort="Boyer, Claude" uniqKey="Boyer C" first="Claude" last="Boyer">Claude Boyer</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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