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HIV-Infected Spleens Present Altered Follicular Helper T Cell (Tfh) Subsets and Skewed B Cell Maturation.

Identifieur interne : 002B28 ( PubMed/Checkpoint ); précédent : 002B27; suivant : 002B29

HIV-Infected Spleens Present Altered Follicular Helper T Cell (Tfh) Subsets and Skewed B Cell Maturation.

Auteurs : Lucie Colineau [France] ; Angeline Rouers [France] ; Takuya Yamamoto [États-Unis] ; Yin Xu [Australie] ; Alejandra Urrutia [France] ; Hang-Phuong Pham [France] ; Sylvain Cardinaud [France] ; Assia Samri [France] ; Karim Dorgham [France] ; Pierre-Grégoire Coulon [France] ; Rémi Cheynier [France] ; Anne Hosmalin [France] ; Eric Oksenhendler [France] ; Adrien Six [France] ; Anthony D. Kelleher [Australie] ; John Zaunders [Australie] ; Richard A. Koup [États-Unis] ; Brigitte Autran [France] ; Arnaud Moris [France] ; Stéphanie Graff-Dubois [France]

Source :

RBID : pubmed:26501424

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English descriptors

Abstract

Follicular helper T (Tfh) cells within secondary lymphoid organs control multiple steps of B cell maturation and antibody (Ab) production. HIV-1 infection is associated with an altered B cell differentiation and Tfh isolated from lymph nodes of HIV-infected (HIV+) individuals provide inadequate B cell help in vitro. However, the mechanisms underlying this impairment of Tfh function are not fully defined. Using a unique collection of splenocytes, we compared the frequency, phenotype and transcriptome of Tfh subsets in spleens from HIV negative (HIV-) and HIV+ subjects. We observed an increase of CXCR5+PD-1highCD57-Tfh and germinal center (GC) CD57+ Tfh in HIV+ spleens. Both subsets showed a reduced mRNA expression of the transcription factor STAT-3, co-stimulatory, regulatory and signal transduction molecules as compared to HIV- spleens. Similarly, Foxp3 expressing follicular regulatory T (Tfr) cells were increased, suggesting sustained GC reactions in chronically HIV+ spleens. As a consequence, GC B cell populations were expanded, however, complete maturation into memory B cells was reduced in HIV+ spleens where we evidenced a compromised production of B cell-activating cytokines such as IL-4 and IL-10. Collectively our data indicate that, although Tfh proliferation and GC reactions seem to be ongoing in HIV-infected spleens, Tfh "differentiation" and expression of costimulatory molecules is skewed with a profound effect on B cell maturation.

DOI: 10.1371/journal.pone.0140978
PubMed: 26501424


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pubmed:26501424

Le document en format XML

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<name sortKey="Moris, Arnaud" sort="Moris, Arnaud" uniqKey="Moris A" first="Arnaud" last="Moris">Arnaud Moris</name>
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<name sortKey="Graff Dubois, Stephanie" sort="Graff Dubois, Stephanie" uniqKey="Graff Dubois S" first="Stéphanie" last="Graff-Dubois">Stéphanie Graff-Dubois</name>
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<title xml:lang="en">HIV-Infected Spleens Present Altered Follicular Helper T Cell (Tfh) Subsets and Skewed B Cell Maturation.</title>
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<name sortKey="Colineau, Lucie" sort="Colineau, Lucie" uniqKey="Colineau L" first="Lucie" last="Colineau">Lucie Colineau</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris</wicri:regionArea>
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<nlm:affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Yamamoto, Takuya" sort="Yamamoto, Takuya" uniqKey="Yamamoto T" first="Takuya" last="Yamamoto">Takuya Yamamoto</name>
<affiliation wicri:level="2">
<nlm:affiliation>Immunology Laboratory, Vaccine research center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Immunology Laboratory, Vaccine research center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Xu, Yin" sort="Xu, Yin" uniqKey="Xu Y" first="Yin" last="Xu">Yin Xu</name>
<affiliation wicri:level="3">
<nlm:affiliation>The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney</wicri:regionArea>
<placeName>
<settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Urrutia, Alejandra" sort="Urrutia, Alejandra" uniqKey="Urrutia A" first="Alejandra" last="Urrutia">Alejandra Urrutia</name>
<affiliation wicri:level="3">
<nlm:affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Pham, Hang Phuong" sort="Pham, Hang Phuong" uniqKey="Pham H" first="Hang-Phuong" last="Pham">Hang-Phuong Pham</name>
<affiliation wicri:level="3">
<nlm:affiliation>Sorbonne Universités UPMC Université Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; CNRS, FRE3632, Immunology-Immunopathology-Immunotherapy (I3), Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités UPMC Université Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; CNRS, FRE3632, Immunology-Immunopathology-Immunotherapy (I3), Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Cardinaud, Sylvain" sort="Cardinaud, Sylvain" uniqKey="Cardinaud S" first="Sylvain" last="Cardinaud">Sylvain Cardinaud</name>
<affiliation wicri:level="3">
<nlm:affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Samri, Assia" sort="Samri, Assia" uniqKey="Samri A" first="Assia" last="Samri">Assia Samri</name>
<affiliation wicri:level="3">
<nlm:affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Dorgham, Karim" sort="Dorgham, Karim" uniqKey="Dorgham K" first="Karim" last="Dorgham">Karim Dorgham</name>
<affiliation wicri:level="3">
<nlm:affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Coulon, Pierre Gregoire" sort="Coulon, Pierre Gregoire" uniqKey="Coulon P" first="Pierre-Grégoire" last="Coulon">Pierre-Grégoire Coulon</name>
<affiliation wicri:level="3">
<nlm:affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Cheynier, Remi" sort="Cheynier, Remi" uniqKey="Cheynier R" first="Rémi" last="Cheynier">Rémi Cheynier</name>
<affiliation wicri:level="4">
<nlm:affiliation>INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Paris-Descartes</orgName>
</affiliation>
</author>
<author>
<name sortKey="Hosmalin, Anne" sort="Hosmalin, Anne" uniqKey="Hosmalin A" first="Anne" last="Hosmalin">Anne Hosmalin</name>
<affiliation wicri:level="4">
<nlm:affiliation>INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Cochin, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Cochin, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Paris-Descartes</orgName>
</affiliation>
</author>
<author>
<name sortKey="Oksenhendler, Eric" sort="Oksenhendler, Eric" uniqKey="Oksenhendler E" first="Eric" last="Oksenhendler">Eric Oksenhendler</name>
<affiliation wicri:level="3">
<nlm:affiliation>Université Paris Diderot, Assistance Publique-Hôpitaux de Paris, Département d'Immunologie Clinique, Hôpital Saint-Louis, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris Diderot, Assistance Publique-Hôpitaux de Paris, Département d'Immunologie Clinique, Hôpital Saint-Louis, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Six, Adrien" sort="Six, Adrien" uniqKey="Six A" first="Adrien" last="Six">Adrien Six</name>
<affiliation wicri:level="3">
<nlm:affiliation>Sorbonne Universités UPMC Université Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; CNRS, FRE3632, Immunology-Immunopathology-Immunotherapy (I3), Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités UPMC Université Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; CNRS, FRE3632, Immunology-Immunopathology-Immunotherapy (I3), Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</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="3">
<nlm:affiliation>The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney</wicri:regionArea>
<placeName>
<settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Zaunders, John" sort="Zaunders, John" uniqKey="Zaunders J" first="John" last="Zaunders">John Zaunders</name>
<affiliation wicri:level="3">
<nlm:affiliation>St. Vincent's Centre for Applied Medical Research, St. Vincent's Hospital, Sydney, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>St. Vincent's Centre for Applied Medical Research, St. Vincent's Hospital, Sydney</wicri:regionArea>
<placeName>
<settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Koup, Richard A" sort="Koup, Richard A" uniqKey="Koup R" first="Richard A" last="Koup">Richard A. Koup</name>
<affiliation wicri:level="2">
<nlm:affiliation>Immunology Laboratory, Vaccine research center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Immunology Laboratory, Vaccine research center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Autran, Brigitte" sort="Autran, Brigitte" uniqKey="Autran B" first="Brigitte" last="Autran">Brigitte Autran</name>
<affiliation wicri:level="3">
<nlm:affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Moris, Arnaud" sort="Moris, Arnaud" uniqKey="Moris A" first="Arnaud" last="Moris">Arnaud Moris</name>
<affiliation wicri:level="3">
<nlm:affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Graff Dubois, Stephanie" sort="Graff Dubois, Stephanie" uniqKey="Graff Dubois S" first="Stéphanie" last="Graff-Dubois">Stéphanie Graff-Dubois</name>
<affiliation wicri:level="3">
<nlm:affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">PloS one</title>
<idno type="eISSN">1932-6203</idno>
<imprint>
<date when="2015" type="published">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>B-Lymphocytes (physiology)</term>
<term>Cell Differentiation (physiology)</term>
<term>Cytokines (analysis)</term>
<term>DNA, Viral (metabolism)</term>
<term>Flow Cytometry</term>
<term>Gene Expression Profiling</term>
<term>HIV Infections (immunology)</term>
<term>HIV Infections (pathology)</term>
<term>Humans</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>STAT3 Transcription Factor (analysis)</term>
<term>Spleen (chemistry)</term>
<term>Spleen (cytology)</term>
<term>Spleen (immunology)</term>
<term>Spleen (pathology)</term>
<term>T-Lymphocytes, Helper-Inducer (physiology)</term>
<term>Virus Integration</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>ADN viral (métabolisme)</term>
<term>Analyse de profil d'expression de gènes</term>
<term>Cytokines (analyse)</term>
<term>Cytométrie en flux</term>
<term>Différenciation cellulaire (physiologie)</term>
<term>Facteur de transcription STAT-3 (analyse)</term>
<term>Humains</term>
<term>Infections à VIH (anatomopathologie)</term>
<term>Infections à VIH (immunologie)</term>
<term>Intégration virale</term>
<term>Lymphocytes B (physiologie)</term>
<term>Lymphocytes T auxiliaires (physiologie)</term>
<term>Rate ()</term>
<term>Rate (anatomopathologie)</term>
<term>Rate (cytologie)</term>
<term>Rate (immunologie)</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en">
<term>Cytokines</term>
<term>STAT3 Transcription Factor</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>DNA, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="analyse" xml:lang="fr">
<term>Cytokines</term>
<term>Facteur de transcription STAT-3</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr">
<term>Infections à VIH</term>
<term>Rate</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en">
<term>Spleen</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr">
<term>Rate</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en">
<term>Spleen</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Infections à VIH</term>
<term>Rate</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>HIV Infections</term>
<term>Spleen</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>ADN viral</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>HIV Infections</term>
<term>Spleen</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr">
<term>Différenciation cellulaire</term>
<term>Lymphocytes B</term>
<term>Lymphocytes T auxiliaires</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en">
<term>B-Lymphocytes</term>
<term>Cell Differentiation</term>
<term>T-Lymphocytes, Helper-Inducer</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Flow Cytometry</term>
<term>Gene Expression Profiling</term>
<term>Humans</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Virus Integration</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Analyse de profil d'expression de gènes</term>
<term>Cytométrie en flux</term>
<term>Humains</term>
<term>Intégration virale</term>
<term>Rate</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
</keywords>
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<front>
<div type="abstract" xml:lang="en">Follicular helper T (Tfh) cells within secondary lymphoid organs control multiple steps of B cell maturation and antibody (Ab) production. HIV-1 infection is associated with an altered B cell differentiation and Tfh isolated from lymph nodes of HIV-infected (HIV+) individuals provide inadequate B cell help in vitro. However, the mechanisms underlying this impairment of Tfh function are not fully defined. Using a unique collection of splenocytes, we compared the frequency, phenotype and transcriptome of Tfh subsets in spleens from HIV negative (HIV-) and HIV+ subjects. We observed an increase of CXCR5+PD-1highCD57-Tfh and germinal center (GC) CD57+ Tfh in HIV+ spleens. Both subsets showed a reduced mRNA expression of the transcription factor STAT-3, co-stimulatory, regulatory and signal transduction molecules as compared to HIV- spleens. Similarly, Foxp3 expressing follicular regulatory T (Tfr) cells were increased, suggesting sustained GC reactions in chronically HIV+ spleens. As a consequence, GC B cell populations were expanded, however, complete maturation into memory B cells was reduced in HIV+ spleens where we evidenced a compromised production of B cell-activating cytokines such as IL-4 and IL-10. Collectively our data indicate that, although Tfh proliferation and GC reactions seem to be ongoing in HIV-infected spleens, Tfh "differentiation" and expression of costimulatory molecules is skewed with a profound effect on B cell maturation.</div>
</front>
</TEI>
<pubmed>
<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">26501424</PMID>
<DateCreated>
<Year>2015</Year>
<Month>10</Month>
<Day>27</Day>
</DateCreated>
<DateCompleted>
<Year>2016</Year>
<Month>06</Month>
<Day>08</Day>
</DateCompleted>
<DateRevised>
<Year>2015</Year>
<Month>10</Month>
<Day>30</Day>
</DateRevised>
<Article PubModel="Electronic-eCollection">
<Journal>
<ISSN IssnType="Electronic">1932-6203</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>10</Volume>
<Issue>10</Issue>
<PubDate>
<Year>2015</Year>
</PubDate>
</JournalIssue>
<Title>PloS one</Title>
<ISOAbbreviation>PLoS ONE</ISOAbbreviation>
</Journal>
<ArticleTitle>HIV-Infected Spleens Present Altered Follicular Helper T Cell (Tfh) Subsets and Skewed B Cell Maturation.</ArticleTitle>
<Pagination>
<MedlinePgn>e0140978</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0140978</ELocationID>
<Abstract>
<AbstractText>Follicular helper T (Tfh) cells within secondary lymphoid organs control multiple steps of B cell maturation and antibody (Ab) production. HIV-1 infection is associated with an altered B cell differentiation and Tfh isolated from lymph nodes of HIV-infected (HIV+) individuals provide inadequate B cell help in vitro. However, the mechanisms underlying this impairment of Tfh function are not fully defined. Using a unique collection of splenocytes, we compared the frequency, phenotype and transcriptome of Tfh subsets in spleens from HIV negative (HIV-) and HIV+ subjects. We observed an increase of CXCR5+PD-1highCD57-Tfh and germinal center (GC) CD57+ Tfh in HIV+ spleens. Both subsets showed a reduced mRNA expression of the transcription factor STAT-3, co-stimulatory, regulatory and signal transduction molecules as compared to HIV- spleens. Similarly, Foxp3 expressing follicular regulatory T (Tfr) cells were increased, suggesting sustained GC reactions in chronically HIV+ spleens. As a consequence, GC B cell populations were expanded, however, complete maturation into memory B cells was reduced in HIV+ spleens where we evidenced a compromised production of B cell-activating cytokines such as IL-4 and IL-10. Collectively our data indicate that, although Tfh proliferation and GC reactions seem to be ongoing in HIV-infected spleens, Tfh "differentiation" and expression of costimulatory molecules is skewed with a profound effect on B cell maturation.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Colineau</LastName>
<ForeName>Lucie</ForeName>
<Initials>L</Initials>
<AffiliationInfo>
<Affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Rouers</LastName>
<ForeName>Angeline</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Yamamoto</LastName>
<ForeName>Takuya</ForeName>
<Initials>T</Initials>
<AffiliationInfo>
<Affiliation>Immunology Laboratory, Vaccine research center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Xu</LastName>
<ForeName>Yin</ForeName>
<Initials>Y</Initials>
<AffiliationInfo>
<Affiliation>The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Urrutia</LastName>
<ForeName>Alejandra</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Pham</LastName>
<ForeName>Hang-Phuong</ForeName>
<Initials>HP</Initials>
<AffiliationInfo>
<Affiliation>Sorbonne Universités UPMC Université Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; CNRS, FRE3632, Immunology-Immunopathology-Immunotherapy (I3), Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Cardinaud</LastName>
<ForeName>Sylvain</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Samri</LastName>
<ForeName>Assia</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Dorgham</LastName>
<ForeName>Karim</ForeName>
<Initials>K</Initials>
<AffiliationInfo>
<Affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Coulon</LastName>
<ForeName>Pierre-Grégoire</ForeName>
<Initials>PG</Initials>
<AffiliationInfo>
<Affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Cheynier</LastName>
<ForeName>Rémi</ForeName>
<Initials>R</Initials>
<AffiliationInfo>
<Affiliation>INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Hosmalin</LastName>
<ForeName>Anne</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Cochin, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Oksenhendler</LastName>
<ForeName>Eric</ForeName>
<Initials>E</Initials>
<AffiliationInfo>
<Affiliation>Université Paris Diderot, Assistance Publique-Hôpitaux de Paris, Département d'Immunologie Clinique, Hôpital Saint-Louis, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Six</LastName>
<ForeName>Adrien</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Sorbonne Universités UPMC Université Paris 06, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; INSERM, UMRS 959, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; CNRS, FRE3632, Immunology-Immunopathology-Immunotherapy (I3), Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kelleher</LastName>
<ForeName>Anthony D</ForeName>
<Initials>AD</Initials>
<AffiliationInfo>
<Affiliation>The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Zaunders</LastName>
<ForeName>John</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>St. Vincent's Centre for Applied Medical Research, St. Vincent's Hospital, Sydney, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Koup</LastName>
<ForeName>Richard A</ForeName>
<Initials>RA</Initials>
<AffiliationInfo>
<Affiliation>Immunology Laboratory, Vaccine research center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, United States of America.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Autran</LastName>
<ForeName>Brigitte</ForeName>
<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Moris</LastName>
<ForeName>Arnaud</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtière, Department of Immunology, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Graff-Dubois</LastName>
<ForeName>Stéphanie</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Sorbonne Universités, UPMC Université Paris 06, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections-CIMI-Paris, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
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<Language>eng</Language>
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<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
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<ArticleDate DateType="Electronic">
<Year>2015</Year>
<Month>10</Month>
<Day>26</Day>
</ArticleDate>
</Article>
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<Country>United States</Country>
<MedlineTA>PLoS One</MedlineTA>
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<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D001402" MajorTopicYN="N">B-Lymphocytes</DescriptorName>
<QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D002454" MajorTopicYN="N">Cell Differentiation</DescriptorName>
<QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName>
<QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004279" MajorTopicYN="N">DNA, Viral</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D005434" MajorTopicYN="N">Flow Cytometry</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D020869" MajorTopicYN="N">Gene Expression Profiling</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D015658" MajorTopicYN="N">HIV Infections</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D060888" MajorTopicYN="N">Real-Time Polymerase Chain Reaction</DescriptorName>
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<DescriptorName UI="D050796" MajorTopicYN="N">STAT3 Transcription Factor</DescriptorName>
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<name sortKey="Yamamoto, Takuya" sort="Yamamoto, Takuya" uniqKey="Yamamoto T" first="Takuya" last="Yamamoto">Takuya Yamamoto</name>
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<name sortKey="Xu, Yin" sort="Xu, Yin" uniqKey="Xu Y" first="Yin" last="Xu">Yin Xu</name>
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