CD4+ T Follicular Helper and IgA+ B Cell Numbers in Gut Biopsies from HIV-Infected Subjects on Antiretroviral Therapy Are Similar to HIV-Uninfected Individuals
Identifieur interne : 000A92 ( Pmc/Checkpoint ); précédent : 000A91; suivant : 000A93CD4+ T Follicular Helper and IgA+ B Cell Numbers in Gut Biopsies from HIV-Infected Subjects on Antiretroviral Therapy Are Similar to HIV-Uninfected Individuals
Auteurs : John Zaunders [Australie] ; Mark Danta [Australie] ; Michelle Bailey [Australie] ; Gerald Mak [Australie] ; Katherine Marks [Australie] ; Nabila Seddiki [France] ; Yin Xu [Australie] ; David J. Templeton [Australie] ; David A. Cooper [Australie] ; Mark A. Boyd [Australie] ; Anthony D. Kelleher [Australie] ; Kersten K. Koelsch [Australie]Source :
- Frontiers in Immunology [ 1664-3224 ] ; 2016.
Abstract
Disruption of gastrointestinal tract epithelial and immune barriers contribute to microbial translocation, systemic inflammation, and progression of HIV-1 infection. Antiretroviral therapy (ART) may lead to reconstitution of CD4+ T cells in gut-associated lymphoid tissue (GALT), but its impact on humoral immunity within GALT is unclear. Therefore, we studied CD4+ subsets, including T follicular helper cells (Tfh), as well as resident B cells that have switched to IgA production, in gut biopsies, from HIV+ subjects on suppressive ART compared to HIV-negative controls (HNC).
Twenty-three HIV+ subjects on ART and 22 HNC undergoing colonoscopy were recruited to the study. Single-cell suspensions were prepared from biopsies from left colon (LC), right colon (RC), and terminal ileum (TI). T and B lymphocyte subsets, as well as EpCAM+ epithelial cells, were accurately enumerated by flow cytometry, using counting beads.
No significant differences in the number of recovered epithelial cells were observed between the two subject groups. However, the median TI CD4+ T cell count/106 epithelial cells was 2.4-fold lower in HIV+ subjects versus HNC (19,679 versus 47,504 cells;
While there were lower absolute CD4+ counts in the TI and LC in HIV+ subjects on ART, they were not associated with significantly reduced Tfh cell counts or IgA+ B cells, suggesting that this important vanguard of adaptive immune defense against luminal microbial products is normalized following ART.
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DOI: 10.3389/fimmu.2016.00438
PubMed: 27822211
PubMed Central: 5075890
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Cooper</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>St Vincent’s Centre for Applied Medical Research, St Vincent’s Hospital</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>The Kirby Institute, The University of New South Wales</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Boyd, Mark A" sort="Boyd, Mark A" uniqKey="Boyd M" first="Mark A." last="Boyd">Mark A. Boyd</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>The Kirby Institute, The University of New South Wales</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kelleher, Anthony D" sort="Kelleher, Anthony D" uniqKey="Kelleher A" first="Anthony D." last="Kelleher">Anthony D. 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Koelsch</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>The Kirby Institute, The University of New South Wales</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27822211</idno><idno type="pmc">5075890</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075890</idno><idno type="RBID">PMC:5075890</idno><idno type="doi">10.3389/fimmu.2016.00438</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">002493</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002493</idno><idno type="wicri:Area/Pmc/Curation">002343</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002343</idno><idno 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Wales</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Danta, Mark" sort="Danta, Mark" uniqKey="Danta M" first="Mark" last="Danta">Mark Danta</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>St Vincent’s Hospital, Clinical School</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bailey, Michelle" sort="Bailey, Michelle" uniqKey="Bailey M" first="Michelle" last="Bailey">Michelle Bailey</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>The Kirby Institute, The University of New South Wales</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mak, Gerald" sort="Mak, Gerald" uniqKey="Mak G" first="Gerald" last="Mak">Gerald Mak</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>St Vincent’s Hospital, Clinical School</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Marks, Katherine" sort="Marks, Katherine" uniqKey="Marks K" first="Katherine" last="Marks">Katherine Marks</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>St Vincent’s Centre for Applied Medical Research, St Vincent’s Hospital</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Seddiki, Nabila" sort="Seddiki, Nabila" uniqKey="Seddiki N" first="Nabila" last="Seddiki">Nabila Seddiki</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Equipe 16, INSERM U955</institution>,<addr-line>Créteil</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Faculté de médecine, Université Paris Est</institution>,<addr-line>Créteil</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Vaccine Research Institute (VRI)</institution>,<addr-line>Créteil</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Xu, Yin" sort="Xu, Yin" uniqKey="Xu Y" first="Yin" last="Xu">Yin Xu</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>The Kirby Institute, The University of New South Wales</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Templeton, David J" sort="Templeton, David J" uniqKey="Templeton D" first="David J." last="Templeton">David J. Templeton</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>The Kirby Institute, The University of New South Wales</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>RPA Sexual Health, Royal Prince Alfred Hospital</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cooper, David A" sort="Cooper, David A" uniqKey="Cooper D" first="David A." last="Cooper">David A. Cooper</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>St Vincent’s Centre for Applied Medical Research, St Vincent’s Hospital</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>The Kirby Institute, The University of New South Wales</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Boyd, Mark A" sort="Boyd, Mark A" uniqKey="Boyd M" first="Mark A." last="Boyd">Mark A. Boyd</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>The Kirby Institute, The University of New South Wales</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kelleher, Anthony D" sort="Kelleher, Anthony D" uniqKey="Kelleher A" first="Anthony D." last="Kelleher">Anthony D. Kelleher</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>St Vincent’s Centre for Applied Medical Research, St Vincent’s Hospital</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>The Kirby Institute, The University of New South Wales</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Koelsch, Kersten K" sort="Koelsch, Kersten K" uniqKey="Koelsch K" first="Kersten K." last="Koelsch">Kersten K. Koelsch</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>The Kirby Institute, The University of New South Wales</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</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="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="ST1"><title>Background</title><p>Disruption of gastrointestinal tract epithelial and immune barriers contribute to microbial translocation, systemic inflammation, and progression of HIV-1 infection. Antiretroviral therapy (ART) may lead to reconstitution of CD4<sup>+</sup> T cells in gut-associated lymphoid tissue (GALT), but its impact on humoral immunity within GALT is unclear. Therefore, we studied CD4<sup>+</sup> subsets, including T follicular helper cells (Tfh), as well as resident B cells that have switched to IgA production, in gut biopsies, from HIV<sup>+</sup> subjects on suppressive ART compared to HIV-negative controls (HNC).</p></sec><sec id="ST2"><title>Methods</title><p>Twenty-three HIV<sup>+</sup> subjects on ART and 22 HNC undergoing colonoscopy were recruited to the study. Single-cell suspensions were prepared from biopsies from left colon (LC), right colon (RC), and terminal ileum (TI). T and B lymphocyte subsets, as well as EpCAM<sup>+</sup> epithelial cells, were accurately enumerated by flow cytometry, using counting beads.</p></sec><sec id="ST3"><title>Results</title><p>No significant differences in the number of recovered epithelial cells were observed between the two subject groups. However, the median TI CD4<sup>+</sup> T cell count/10<sup>6</sup> epithelial cells was 2.4-fold lower in HIV<sup>+</sup> subjects versus HNC (19,679 versus 47,504 cells; <italic>p</italic> = 0.02). Similarly, median LC CD4<sup>+</sup> T cell counts were reduced in HIV<sup>+</sup> subjects (8,358 versus 18,577; <italic>p</italic> = 0.03) but were not reduced in RC. Importantly, we found no significant differences in Tfh or IgA<sup>+</sup> B cell counts at either site between HIV<sup>+</sup> subjects and HNC. Further analysis showed no difference in CD4<sup>+</sup>, Tfh, or IgA<sup>+</sup> B cell counts between subjects who commenced ART in primary compared to chronic HIV-1 infection. Despite the decrease in total CD4 T cells, we could not identify a selective decrease of other key subsets of CD4<sup>+</sup> T cells, including CCR5<sup>+</sup> cells, CD127<sup>+</sup> long-term memory cells, CD103<sup>+</sup> tissue-resident cells, or CD161<sup>+</sup> cells (surrogate marker for Th17), but there was a slight increase in the proportion of T regulatory cells.</p></sec><sec id="ST4"><title>Conclusion</title><p>While there were lower absolute CD4<sup>+</sup> counts in the TI and LC in HIV<sup>+</sup> subjects on ART, they were not associated with significantly reduced Tfh cell counts or IgA<sup>+</sup> B cells, suggesting that this important vanguard of adaptive immune defense against luminal microbial products is normalized following ART.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Douek, D" uniqKey="Douek D">D Douek</name></author></analytic></biblStruct><biblStruct><analytic><author><name 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uniqKey="Mcbride K">K McBride</name></author><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y Xu</name></author><author><name sortKey="Bailey, M" uniqKey="Bailey M">M Bailey</name></author><author><name sortKey="Seddiki, N" uniqKey="Seddiki N">N Seddiki</name></author><author><name sortKey="Suzuki, K" uniqKey="Suzuki K">K Suzuki</name></author><author><name sortKey="Gao, Y" uniqKey="Gao Y">Y Gao</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">Front Immunol</journal-id><journal-id journal-id-type="iso-abbrev">Front Immunol</journal-id><journal-id journal-id-type="publisher-id">Front. Immunol.</journal-id><journal-title-group><journal-title>Frontiers in Immunology</journal-title></journal-title-group><issn pub-type="epub">1664-3224</issn><publisher><publisher-name>Frontiers Media S.A.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27822211</article-id><article-id pub-id-type="pmc">5075890</article-id><article-id pub-id-type="doi">10.3389/fimmu.2016.00438</article-id><article-categories><subj-group subj-group-type="heading"><subject>Immunology</subject><subj-group><subject>Original Research</subject></subj-group></subj-group></article-categories><title-group><article-title>CD4<sup>+</sup> T Follicular Helper and IgA<sup>+</sup> B Cell Numbers in Gut Biopsies from HIV-Infected Subjects on Antiretroviral Therapy Are Similar to HIV-Uninfected Individuals</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zaunders</surname><given-names>John</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="corresp" rid="cor1">*</xref><xref ref-type="author-notes" rid="fn001"><sup>†</sup></xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/74084"></uri></contrib><contrib contrib-type="author"><name><surname>Danta</surname><given-names>Mark</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="author-notes" rid="fn001"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bailey</surname><given-names>Michelle</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mak</surname><given-names>Gerald</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/364420"></uri></contrib><contrib contrib-type="author"><name><surname>Marks</surname><given-names>Katherine</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/382469"></uri></contrib><contrib contrib-type="author"><name><surname>Seddiki</surname><given-names>Nabila</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="aff" rid="aff5"><sup>5</sup></xref><xref ref-type="aff" rid="aff6"><sup>6</sup></xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/200924"></uri></contrib><contrib contrib-type="author"><name><surname>Xu</surname><given-names>Yin</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/200974"></uri></contrib><contrib contrib-type="author"><name><surname>Templeton</surname><given-names>David J.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff7"><sup>7</sup></xref><xref ref-type="author-notes" rid="fn001"><sup>§</sup></xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/217192"></uri></contrib><contrib contrib-type="author"><name><surname>Cooper</surname><given-names>David A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Boyd</surname><given-names>Mark A.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kelleher</surname><given-names>Anthony D.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="author-notes" rid="fn002"><sup>‡</sup></xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/307144"></uri></contrib><contrib contrib-type="author"><name><surname>Koelsch</surname><given-names>Kersten K.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="corresp" rid="cor1">*</xref><xref ref-type="author-notes" rid="fn002"><sup>‡</sup></xref><uri xlink:type="simple" xlink:href="http://frontiersin.org/people/u/268707"></uri></contrib></contrib-group><aff id="aff1"><sup>1</sup><institution>St Vincent’s Centre for Applied Medical Research, St Vincent’s Hospital</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></aff><aff id="aff2"><sup>2</sup><institution>The Kirby Institute, The University of New South Wales</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></aff><aff id="aff3"><sup>3</sup><institution>St Vincent’s Hospital, Clinical School</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></aff><aff id="aff4"><sup>4</sup><institution>Equipe 16, INSERM U955</institution>,<addr-line>Créteil</addr-line>,<country>France</country></aff><aff id="aff5"><sup>5</sup><institution>Faculté de médecine, Université Paris Est</institution>,<addr-line>Créteil</addr-line>,<country>France</country></aff><aff id="aff6"><sup>6</sup><institution>Vaccine Research Institute (VRI)</institution>,<addr-line>Créteil</addr-line>,<country>France</country></aff><aff id="aff7"><sup>7</sup><institution>RPA Sexual Health, Royal Prince Alfred Hospital</institution>,<addr-line>Sydney, NSW</addr-line>,<country>Australia</country></aff><author-notes><fn fn-type="edited-by"><p>Edited by: Eric Cox, Ghent University, Belgium</p></fn><fn fn-type="edited-by"><p>Reviewed by: Nicolaas Adrianus Bos, University Medical Center Groningen, Netherlands; Rita Carsetti, Bambino Gesù Children’s Hospital (IRCCS), Italy</p></fn><corresp content-type="corresp" id="cor1">*Correspondence: John Zaunders, <email>j.zaunders@amr.org.au</email>; Kersten K. Koelsch, <email>kkoelsch@kirby.unsw.edu.au</email></corresp><fn fn-type="present-address" id="fn001"><p><sup>†</sup>John Zaunders and Mark Danta are equal first authors.</p></fn><fn fn-type="present-address" id="fn002"><p><sup>‡</sup>Anthony D. Kelleher and Kersten K. Koelsch are equal senior authors.</p></fn><fn fn-type="present-address" id="fn003"><p><sup>§</sup>Present address: David J. Templeton, Central Clinical School, The University of Sydney, Sydney, NSW, Australia</p></fn><fn fn-type="other" id="fn004"><p>Specialty section: This article was submitted to Mucosal Immunity, a section of the journal Frontiers in Immunology</p></fn></author-notes><pub-date pub-type="epub"><day>24</day><month>10</month><year>2016</year></pub-date><pub-date pub-type="collection"><year>2016</year></pub-date><volume>7</volume><elocation-id>438</elocation-id><history><date date-type="received"><day>28</day><month>5</month><year>2016</year></date><date date-type="accepted"><day>04</day><month>10</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2016 Zaunders, Danta, Bailey, Mak, Marks, Seddiki, Xu, Templeton, Cooper, Boyd, Kelleher and Koelsch.</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>Zaunders, Danta, Bailey, Mak, Marks, Seddiki, Xu, Templeton, Cooper, Boyd, Kelleher and Koelsch</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license></permissions><abstract abstract-type="executive-summary"><sec id="ST1"><title>Background</title><p>Disruption of gastrointestinal tract epithelial and immune barriers contribute to microbial translocation, systemic inflammation, and progression of HIV-1 infection. Antiretroviral therapy (ART) may lead to reconstitution of CD4<sup>+</sup> T cells in gut-associated lymphoid tissue (GALT), but its impact on humoral immunity within GALT is unclear. Therefore, we studied CD4<sup>+</sup> subsets, including T follicular helper cells (Tfh), as well as resident B cells that have switched to IgA production, in gut biopsies, from HIV<sup>+</sup> subjects on suppressive ART compared to HIV-negative controls (HNC).</p></sec><sec id="ST2"><title>Methods</title><p>Twenty-three HIV<sup>+</sup> subjects on ART and 22 HNC undergoing colonoscopy were recruited to the study. Single-cell suspensions were prepared from biopsies from left colon (LC), right colon (RC), and terminal ileum (TI). T and B lymphocyte subsets, as well as EpCAM<sup>+</sup> epithelial cells, were accurately enumerated by flow cytometry, using counting beads.</p></sec><sec id="ST3"><title>Results</title><p>No significant differences in the number of recovered epithelial cells were observed between the two subject groups. However, the median TI CD4<sup>+</sup> T cell count/10<sup>6</sup> epithelial cells was 2.4-fold lower in HIV<sup>+</sup> subjects versus HNC (19,679 versus 47,504 cells; <italic>p</italic> = 0.02). Similarly, median LC CD4<sup>+</sup> T cell counts were reduced in HIV<sup>+</sup> subjects (8,358 versus 18,577; <italic>p</italic> = 0.03) but were not reduced in RC. Importantly, we found no significant differences in Tfh or IgA<sup>+</sup> B cell counts at either site between HIV<sup>+</sup> subjects and HNC. Further analysis showed no difference in CD4<sup>+</sup>, Tfh, or IgA<sup>+</sup> B cell counts between subjects who commenced ART in primary compared to chronic HIV-1 infection. Despite the decrease in total CD4 T cells, we could not identify a selective decrease of other key subsets of CD4<sup>+</sup> T cells, including CCR5<sup>+</sup> cells, CD127<sup>+</sup> long-term memory cells, CD103<sup>+</sup> tissue-resident cells, or CD161<sup>+</sup> cells (surrogate marker for Th17), but there was a slight increase in the proportion of T regulatory cells.</p></sec><sec id="ST4"><title>Conclusion</title><p>While there were lower absolute CD4<sup>+</sup> counts in the TI and LC in HIV<sup>+</sup> subjects on ART, they were not associated with significantly reduced Tfh cell counts or IgA<sup>+</sup> B cells, suggesting that this important vanguard of adaptive immune defense against luminal microbial products is normalized following ART.</p></sec></abstract><kwd-group><kwd>HIV</kwd><kwd>gut-associated lymphoid tissue</kwd><kwd>CD4<sup>+</sup> T lymphocytes</kwd><kwd>T follicular helper cells</kwd><kwd>germinal centers</kwd><kwd>IgA B cells</kwd></kwd-group><funding-group><award-group><funding-source id="cn01">National Health and Medical Research Council<named-content content-type="fundref-id">10.13039/501100000925</named-content></funding-source><award-id rid="cn01">1052979</award-id></award-group><award-group><funding-source id="cn02">St Vincent’s Clinic Foundation</funding-source><award-id rid="cn02">AG 4 2012</award-id></award-group></funding-group><counts><fig-count count="5"></fig-count><table-count count="0"></table-count><equation-count count="0"></equation-count><ref-count count="62"></ref-count><page-count count="12"></page-count><word-count count="8021"></word-count></counts></article-meta></front></pmc><affiliations><list><country><li>Australie</li><li>France</li></country></list><tree><country name="Australie"><noRegion><name sortKey="Zaunders, John" sort="Zaunders, John" uniqKey="Zaunders J" first="John" last="Zaunders">John Zaunders</name></noRegion><name sortKey="Bailey, Michelle" sort="Bailey, Michelle" uniqKey="Bailey M" first="Michelle" last="Bailey">Michelle Bailey</name><name sortKey="Boyd, Mark A" sort="Boyd, Mark A" uniqKey="Boyd M" first="Mark A." last="Boyd">Mark A. Boyd</name><name sortKey="Cooper, David A" sort="Cooper, David A" uniqKey="Cooper D" first="David A." last="Cooper">David A. Cooper</name><name sortKey="Cooper, David A" sort="Cooper, David A" uniqKey="Cooper D" first="David A." last="Cooper">David A. Cooper</name><name sortKey="Danta, Mark" sort="Danta, Mark" uniqKey="Danta M" first="Mark" last="Danta">Mark Danta</name><name sortKey="Kelleher, Anthony D" sort="Kelleher, Anthony D" uniqKey="Kelleher A" first="Anthony D." last="Kelleher">Anthony D. Kelleher</name><name sortKey="Kelleher, Anthony D" sort="Kelleher, Anthony D" uniqKey="Kelleher A" first="Anthony D." last="Kelleher">Anthony D. Kelleher</name><name sortKey="Koelsch, Kersten K" sort="Koelsch, Kersten K" uniqKey="Koelsch K" first="Kersten K." last="Koelsch">Kersten K. Koelsch</name><name sortKey="Mak, Gerald" sort="Mak, Gerald" uniqKey="Mak G" first="Gerald" last="Mak">Gerald Mak</name><name sortKey="Marks, Katherine" sort="Marks, Katherine" uniqKey="Marks K" first="Katherine" last="Marks">Katherine Marks</name><name sortKey="Templeton, David J" sort="Templeton, David J" uniqKey="Templeton D" first="David J." last="Templeton">David J. Templeton</name><name sortKey="Templeton, David J" sort="Templeton, David J" uniqKey="Templeton D" first="David J." last="Templeton">David J. Templeton</name><name sortKey="Xu, Yin" sort="Xu, Yin" uniqKey="Xu Y" first="Yin" last="Xu">Yin Xu</name><name sortKey="Zaunders, John" sort="Zaunders, John" uniqKey="Zaunders J" first="John" last="Zaunders">John Zaunders</name></country><country name="France"><noRegion><name sortKey="Seddiki, Nabila" sort="Seddiki, Nabila" uniqKey="Seddiki N" first="Nabila" last="Seddiki">Nabila Seddiki</name></noRegion><name sortKey="Seddiki, Nabila" sort="Seddiki, Nabila" uniqKey="Seddiki N" first="Nabila" last="Seddiki">Nabila Seddiki</name><name sortKey="Seddiki, Nabila" sort="Seddiki, Nabila" uniqKey="Seddiki N" first="Nabila" last="Seddiki">Nabila Seddiki</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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