Journal
IMMUNITY
Volume 39, Issue 4, Pages 770-781Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2013.09.007
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Funding
- National Basic Research Program of China (973 Program) [2010CB529100]
- National Health and Medical Research Council (NHMRC) [1010761]
- Australian Research Council [DP110105024]
- Ramaciotti Foundation
- National Natural Science Foundation of China (NSFC) [81128012]
- Beijing Natural Science Foundation [7131015]
- NSFC [3107088]
- NHMRC program
- NHMRC Fellowship [GNT1011947]
- Monash Fellowship
- Viertel Senior Medical Research Fellowship
- NHMRC Australian Fellowship
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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 anti-body 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.
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