Circulating precursor CCR7loPD-1hi CXCR5+ CD4+ T cells indicate tfh cell activity and promote antibody responses upon antigen reexposure

Jing He, Louis M. Tsai, Yew Ann Leong, Xin Hu, Cindy S. Ma, Nina Chevalier, Xiaolin Sun, Kirsten Vandenberg, Steve Rockman, Yan Ding, Lei Zhu, Wei Wei, Changqi Wang, Alexander Karnowski, Gabrielle T. Belz, Joanna R. Ghali, Matthew C. Cook, D. Sean Riminton, André Veillette, Pamela L. SchwartzbergFabienne Mackay, Robert Brink, Stuart G. Tangye, Carola G. Vinuesa, Charles R. Mackay, Zhanguo Li*, Di Yu

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    537 Citations (Scopus)

    Abstract

    Follicular B helper T (Tfh) cells support high affinity and long-term antibody responses. Here we found that within circulating CXCR5+ CD4+ Tcells in humans and mice, the CCR7loPD-1hi subset has a partial Tfh effector phenotype, whereas CCR7hiPD-1lo cells have a resting phenotype. The circulating CCR7loPD-1hi subset was indicative of active Tfh differentiation in lymphoid organs and correlated with clinical indices in autoimmune diseases. Thus the CCR7loPD-1hi subset provides a biomarker to monitor protective antibody responses during infection or vaccination and pathogenic antibody responses in autoimmune diseases. Differentiation of both CCR7hiPD-1lo and CCR7loPD-1hi subsets required ICOS and BCL6, but not SAP, suggesting that circulating CXCR5+ helper Tcells are primarily generated before germinal centers. Upon antigen reencounter, CCR7loPD-1hi CXCR5+ precursors rapidly differentiate into mature Tfh cells to promote antibody responses. Therefore, circulating CCR7loPD-1hi CXCR5+ CD4+ Tcells are generated during active Tfh differentiation and represent a new mechanism of immunological early memory.

    Original languageEnglish
    Pages (from-to)770-781
    Number of pages12
    JournalImmunity
    Volume39
    Issue number4
    DOIs
    Publication statusPublished - 17 Oct 2013

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