Circulating precursor CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure

Jing He, Louis M Tsai, Yew A Leong, Xin Jack 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, Sean Riminton, Andre Veillette, Pamela L SchwartzbergFabienne Mackay, Robert Brink, Stuart G Tangye, Carola G Vinuesa, Charles R Mackay, Zhan Guo Li, Di Yu

Research output: Contribution to journalArticleResearchpeer-review

353 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(+) T cells in humans and mice, the CCR7(lo)PD-1(hi) subset has a partial Tfh effector phenotype, whereas CCR7(hi)PD-1(lo) cells have a resting phenotype. The circulating CCR7(lo)PD-1(hi) subset was indicative of active Tfh differentiation in lymphoid organs and correlated with clinical indices in autoimmune diseases. Thus the CCR7(lo)PD-1(hi) subset provides a biomarker to monitor protective antibody responses during infection or vaccination and pathogenic antibody responses in autoimmune diseases. Differentiation of both CCR7(hi)PD-1(lo) and CCR7(lo)PD-1(hi) subsets required ICOS and BCL6, but not SAP, suggesting that circulating CXCR5(+) helper T cells are primarily generated before germinal centers. Upon antigen reencounter, CCR7(lo)PD-1(hi) CXCR5(+) precursors rapidly differentiate into mature Tfh cells to promote antibody responses. Therefore, circulating CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells 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
DOIs
Publication statusPublished - 2013

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