CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses

Nina Chevalier, David Jarrossay, Edwin Ho, Danielle T Avery, Cindy S Ma, Di Yu, Federica Sallusto, Stuart G Tangye, Charles Reay Mackay

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    201 Citations (Scopus)

    Abstract

    High expression of CXCR5 is one of the defining hallmarks of T follicular helper cells (T(FH)), a CD4 Th cell subset that promotes germinal center reactions and the selection and affinity maturation of B cells. CXCR5 is also expressed on 20-25 of peripheral blood human central memory CD4 T cells (T(CM)), although the definitive function of these cells is not fully understood. The constitutive expression of CXCR5 on T(FH) cells and a fraction of circulating T(CM) suggests that CXCR5(+) T(CM) may represent a specialized subset of memory-type T(FH) cells programmed for homing to follicles and providing B cell help. To verify this assumption, we analyzed this cell population and show its specialized function in supporting humoral immune responses. Compared with their CXCR5(-) T(CM) counterparts, CXCR5(+) T(CM) expressed high levels of the chemokine CXCL13 and efficiently induced plasma cell differentiation and Ig secretion. We found that the distinct B cell helper qualities of CXCR5(+) T(CM) were mainly due to high ICOS expression and pronounced responsiveness to ICOS ligand costimulation together with large IL-10 secretion. Furthermore, B cell helper attributes of CXCR5(+) T(CM) were almost exclusively acquired on cognate interaction with B cells, but not with dendritic cells. This implies that a preferential recruitment of circulating CXCR5(+) T(CM) to CXCL13-rich B cell follicles is required for the promotion of a quick and efficient protective secondary humoral immune response. Taken together, we propose that CXCR5(+) T(CM) represent a distinct memory cell subset specialized in supporting Ab-mediated immune responses.
    Original languageEnglish
    Pages (from-to)5556 - 5568
    Number of pages13
    JournalJournal of Immunology
    Volume186
    Issue number10
    DOIs
    Publication statusPublished - 2011

    Cite this

    Chevalier, Nina ; Jarrossay, David ; Ho, Edwin ; Avery, Danielle T ; Ma, Cindy S ; Yu, Di ; Sallusto, Federica ; Tangye, Stuart G ; Mackay, Charles Reay. / CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses. In: Journal of Immunology. 2011 ; Vol. 186, No. 10. pp. 5556 - 5568.
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    title = "CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses",
    abstract = "High expression of CXCR5 is one of the defining hallmarks of T follicular helper cells (T(FH)), a CD4 Th cell subset that promotes germinal center reactions and the selection and affinity maturation of B cells. CXCR5 is also expressed on 20-25 of peripheral blood human central memory CD4 T cells (T(CM)), although the definitive function of these cells is not fully understood. The constitutive expression of CXCR5 on T(FH) cells and a fraction of circulating T(CM) suggests that CXCR5(+) T(CM) may represent a specialized subset of memory-type T(FH) cells programmed for homing to follicles and providing B cell help. To verify this assumption, we analyzed this cell population and show its specialized function in supporting humoral immune responses. Compared with their CXCR5(-) T(CM) counterparts, CXCR5(+) T(CM) expressed high levels of the chemokine CXCL13 and efficiently induced plasma cell differentiation and Ig secretion. We found that the distinct B cell helper qualities of CXCR5(+) T(CM) were mainly due to high ICOS expression and pronounced responsiveness to ICOS ligand costimulation together with large IL-10 secretion. Furthermore, B cell helper attributes of CXCR5(+) T(CM) were almost exclusively acquired on cognate interaction with B cells, but not with dendritic cells. This implies that a preferential recruitment of circulating CXCR5(+) T(CM) to CXCL13-rich B cell follicles is required for the promotion of a quick and efficient protective secondary humoral immune response. Taken together, we propose that CXCR5(+) T(CM) represent a distinct memory cell subset specialized in supporting Ab-mediated immune responses.",
    author = "Nina Chevalier and David Jarrossay and Edwin Ho and Avery, {Danielle T} and Ma, {Cindy S} and Di Yu and Federica Sallusto and Tangye, {Stuart G} and Mackay, {Charles Reay}",
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    Chevalier, N, Jarrossay, D, Ho, E, Avery, DT, Ma, CS, Yu, D, Sallusto, F, Tangye, SG & Mackay, CR 2011, 'CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses', Journal of Immunology, vol. 186, no. 10, pp. 5556 - 5568. https://doi.org/10.4049/jimmunol.1002828

    CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses. / Chevalier, Nina; Jarrossay, David; Ho, Edwin; Avery, Danielle T; Ma, Cindy S; Yu, Di; Sallusto, Federica; Tangye, Stuart G; Mackay, Charles Reay.

    In: Journal of Immunology, Vol. 186, No. 10, 2011, p. 5556 - 5568.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses

    AU - Chevalier, Nina

    AU - Jarrossay, David

    AU - Ho, Edwin

    AU - Avery, Danielle T

    AU - Ma, Cindy S

    AU - Yu, Di

    AU - Sallusto, Federica

    AU - Tangye, Stuart G

    AU - Mackay, Charles Reay

    PY - 2011

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    AB - High expression of CXCR5 is one of the defining hallmarks of T follicular helper cells (T(FH)), a CD4 Th cell subset that promotes germinal center reactions and the selection and affinity maturation of B cells. CXCR5 is also expressed on 20-25 of peripheral blood human central memory CD4 T cells (T(CM)), although the definitive function of these cells is not fully understood. The constitutive expression of CXCR5 on T(FH) cells and a fraction of circulating T(CM) suggests that CXCR5(+) T(CM) may represent a specialized subset of memory-type T(FH) cells programmed for homing to follicles and providing B cell help. To verify this assumption, we analyzed this cell population and show its specialized function in supporting humoral immune responses. Compared with their CXCR5(-) T(CM) counterparts, CXCR5(+) T(CM) expressed high levels of the chemokine CXCL13 and efficiently induced plasma cell differentiation and Ig secretion. We found that the distinct B cell helper qualities of CXCR5(+) T(CM) were mainly due to high ICOS expression and pronounced responsiveness to ICOS ligand costimulation together with large IL-10 secretion. Furthermore, B cell helper attributes of CXCR5(+) T(CM) were almost exclusively acquired on cognate interaction with B cells, but not with dendritic cells. This implies that a preferential recruitment of circulating CXCR5(+) T(CM) to CXCL13-rich B cell follicles is required for the promotion of a quick and efficient protective secondary humoral immune response. Taken together, we propose that CXCR5(+) T(CM) represent a distinct memory cell subset specialized in supporting Ab-mediated immune responses.

    UR - http://www.jimmunol.org/content/186/10/5556.full.pdf+html

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    DO - 10.4049/jimmunol.1002828

    M3 - Article

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    EP - 5568

    JO - Journal of Immunology

    JF - Journal of Immunology

    SN - 0022-1767

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