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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


He, J; Tsai, LM; Leong, YA; Hu, X; Ma, CS; Chevalier, N; Sun, X; Vandenberg, K; Rockman, S; Ding, Y; Zhu, L; Wei, W; Wang, C; Karnowski, A; Belz, GT; Ghali, JR; Cook, MC; Riminton, DS; Veillette, A; Schwartzberg, PL; Mackay, F; Brink, R; Tangye, SG; Vinuesa, CG; Mackay, CR; Li, Z; Yu, D
2013-10-17
Immunity
Journal Article
39
4
770-81
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.
CELL PRESS
Animals; Antibodies/*immunology; Antigens/immunology; B-Lymphocytes/immunology/pathology/virology; Cell Differentiation; DNA-Binding Proteins/genetics/immunology; Gene Expression; Germinal Center/immunology/pathology/virology; Humans; Immunity, Humoral; *Immunologic Memory; Immunophenotyping; Inducible T-Cell Co-Stimulator Protein/genetics/immunology; Mice; Programmed Cell Death 1 Receptor/genetics/*immunology; Receptors, CXCR/genetics/*immunology; Receptors, CXCR5/genetics/*immunology; T-Lymphocytes, Helper-Inducer/*immunology/pathology/virology
Molecular Immunology
10.1016/j.immuni.2013.09.007
Copyright © 2013 Elsevier Inc. All rights reserved.

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Creation Date 2014-02-18 03:39:53