The PD-1/PD-L1 Pathway Affects the Expansion and Function of Cytotoxic CD8+ T Cells During an Acute Retroviral Infection
Identifieur interne : 000629 ( Main/Exploration ); précédent : 000628; suivant : 000630The PD-1/PD-L1 Pathway Affects the Expansion and Function of Cytotoxic CD8+ T Cells During an Acute Retroviral Infection
Auteurs : Paul David [Allemagne] ; Dominik A. Megger [Allemagne] ; Tamara Kaiser [Allemagne] ; Tanja Werner [Allemagne] ; Jia Liu [Allemagne, République populaire de Chine] ; Lieping Chen [États-Unis] ; Barbara Sitek [Allemagne] ; Ulf Dittmer [Allemagne] ; Gennadiy Zelinskyy [Allemagne]Source :
- Frontiers in Immunology [ 1664-3224 ] ; 2019.
Abstract
Cytotoxic CD8+ T lymphocytes (CTL) efficiently control acute virus infections but can become exhausted when a chronic infection develops. The checkpoint receptor PD-1 suppresses the functionality of virus-specific CD8+ T cells during chronic infection. However, the role of the PD-L1/PD-1 pathway during the acute phase of infections has not been well characterized. In the current study the effects of PD-1 or PD-L1 deficiency on the CD8+ T cell response against Friend retroviral (FV) infection of knockout mice was analyzed during acute infection. We observed an enhanced proliferation, functional maturation, and reduced apoptosis of effector CD8+ T cells in the absence of PD-1 or PD-L1. The knockout of PD-L1 had a stronger effect on the functionality of CD8+ T cells than that of PD-1. Augmented CTL responses were associated with an improved control of FV replication. The strong phenotype of FV-infected PD-L1 knockout mice was independent of the interaction with CD80 as an additional receptor for PD-L1. Furthermore, we performed a detailed analysis of the production of different granzymes in virus-specific CD8+ T cells and observed that especially the simultaneous production of multiple granzymes in individual T cells (multifunctionality) was under the control of the PD-1/PD-L1 pathway. The findings from this study allow for a better understanding of the development of antiviral cytotoxic immunity during acute viral infections.
Url:
DOI: 10.3389/fimmu.2019.00054
PubMed: 30804928
PubMed Central: 6370637
Affiliations:
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strict</wicri:regionArea></affiliation></author><author><name sortKey="Megger, Dominik A" sort="Megger, Dominik A" uniqKey="Megger D" first="Dominik A." last="Megger">Dominik A. Megger</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Medizinisches Proteom-Center, Ruhr-Universität Bochum</institution>,<addr-line>Bochum</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kaiser, Tamara" sort="Kaiser, Tamara" uniqKey="Kaiser T" first="Tamara" last="Kaiser">Tamara Kaiser</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Virology, University Hospital Essen, University of Duisburg-Essen</institution>,<addr-line>Essen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Werner, Tanja" sort="Werner, Tanja" uniqKey="Werner T" first="Tanja" last="Werner">Tanja Werner</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Virology, University Hospital Essen, University of Duisburg-Essen</institution>,<addr-line>Essen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Jia" sort="Liu, Jia" uniqKey="Liu J" first="Jia" last="Liu">Jia Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Virology, University Hospital Essen, University of Duisburg-Essen</institution>,<addr-line>Essen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology</institution>,<addr-line>Wuhan</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Lieping" sort="Chen, Lieping" uniqKey="Chen L" first="Lieping" last="Chen">Lieping Chen</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Department of Immunobiology, Yale School of Medicine, Yale University</institution>,<addr-line>New Haven, CT</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sitek, Barbara" sort="Sitek, Barbara" uniqKey="Sitek B" first="Barbara" last="Sitek">Barbara Sitek</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Medizinisches Proteom-Center, Ruhr-Universität Bochum</institution>,<addr-line>Bochum</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></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="aff1"><institution>Institute for Virology, University Hospital Essen, University of Duisburg-Essen</institution>,<addr-line>Essen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zelinskyy, Gennadiy" sort="Zelinskyy, Gennadiy" uniqKey="Zelinskyy G" first="Gennadiy" last="Zelinskyy">Gennadiy Zelinskyy</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Institute for Virology, University Hospital Essen, University of Duisburg-Essen</institution>,<addr-line>Essen</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Immunology</title><idno type="eISSN">1664-3224</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Cytotoxic CD8<sup>+</sup> T lymphocytes (CTL) efficiently control acute virus infections but can become exhausted when a chronic infection develops. The checkpoint receptor PD-1 suppresses the functionality of virus-specific CD8<sup>+</sup> T cells during chronic infection. However, the role of the PD-L1/PD-1 pathway during the acute phase of infections has not been well characterized. In the current study the effects of PD-1 or PD-L1 deficiency on the CD8<sup>+</sup> T cell response against Friend retroviral (FV) infection of knockout mice was analyzed during acute infection. We observed an enhanced proliferation, functional maturation, and reduced apoptosis of effector CD8<sup>+</sup> T cells in the absence of PD-1 or PD-L1. The knockout of PD-L1 had a stronger effect on the functionality of CD8<sup>+</sup> T cells than that of PD-1. Augmented CTL responses were associated with an improved control of FV replication. The strong phenotype of FV-infected PD-L1 knockout mice was independent of the interaction with CD80 as an additional receptor for PD-L1. Furthermore, we performed a detailed analysis of the production of different granzymes in virus-specific CD8<sup>+</sup> T cells and observed that especially the simultaneous production of multiple granzymes in individual T cells (multifunctionality) was under the control of the PD-1/PD-L1 pathway. The findings from this study allow for a better understanding of the development of antiviral cytotoxic immunity during acute viral infections.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Sharpe, Ah" uniqKey="Sharpe A">AH Sharpe</name></author><author><name sortKey="Wherry, Ej" uniqKey="Wherry E">EJ Wherry</name></author><author><name sortKey="Ahmed, R" uniqKey="Ahmed R">R Ahmed</name></author><author><name sortKey="Freeman, Gj" uniqKey="Freeman G">GJ Freeman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barber, Dl" uniqKey="Barber D">DL Barber</name></author><author><name sortKey="Wherry, Ej" uniqKey="Wherry E">EJ Wherry</name></author><author><name sortKey="Masopust, D" uniqKey="Masopust D">D Masopust</name></author><author><name sortKey="Zhu, B" uniqKey="Zhu B">B Zhu</name></author><author><name sortKey="Allison, Jp" uniqKey="Allison J">JP Allison</name></author><author><name 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Paul" uniqKey="David P" first="Paul" last="David">Paul David</name></noRegion><name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name><name sortKey="Kaiser, Tamara" sort="Kaiser, Tamara" uniqKey="Kaiser T" first="Tamara" last="Kaiser">Tamara Kaiser</name><name sortKey="Liu, Jia" sort="Liu, Jia" uniqKey="Liu J" first="Jia" last="Liu">Jia Liu</name><name sortKey="Megger, Dominik A" sort="Megger, Dominik A" uniqKey="Megger D" first="Dominik A." last="Megger">Dominik A. Megger</name><name sortKey="Sitek, Barbara" sort="Sitek, Barbara" uniqKey="Sitek B" first="Barbara" last="Sitek">Barbara Sitek</name><name sortKey="Werner, Tanja" sort="Werner, Tanja" uniqKey="Werner T" first="Tanja" last="Werner">Tanja Werner</name><name sortKey="Zelinskyy, Gennadiy" sort="Zelinskyy, Gennadiy" uniqKey="Zelinskyy G" first="Gennadiy" last="Zelinskyy">Gennadiy Zelinskyy</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Liu, Jia" sort="Liu, Jia" uniqKey="Liu J" first="Jia" last="Liu">Jia Liu</name></noRegion></country><country name="États-Unis"><noRegion><name sortKey="Chen, Lieping" sort="Chen, Lieping" uniqKey="Chen L" first="Lieping" last="Chen">Lieping Chen</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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