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


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.

Type Journal
Authors He, J.; Tsai, L. M.; Leong, Y. A.; Hu, X.; Ma, C. S.; Chevalier, N.; Sun, X.; Vandenberg, K.; Rockman, S.; Ding, Y.; Zhu, L.; Wei, W.; Wang, C.; Karnowski, A.; Belz, G. T.; Ghali, J. R.; Cook, M. C.; Riminton, D. S.; Veillette, A.; Schwartzberg, P. L.; Mackay, F.; Brink, R.; Tangye, S. G.; Vinuesa, C. G.; Mackay, C. R.; Li, Z.; Yu, D.;
Publisher Name IMMUNITY
Published Date 2013-10-18
Published Volume 39
Published Issue 4
Published Pages 770-81
Status Published in-print
DOI 10.1016/j.immuni.2013.09.007
URL link to publisher's version
OpenAccess link to author's accepted manuscript version