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 language | English |
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Pages (from-to) | 770-781 |
Number of pages | 12 |
Journal | Immunity |
Volume | 39 |
Issue number | 4 |
DOIs | |
Publication status | Published - 17 Oct 2013 |