Circulating precursor CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure
Publication Year 2013-10-17, Volume 39, Issue #4, Page 770-81
Journal Title
Publication Type
Journal Article
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.
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
WEHI Research Division(s)
Molecular Immunology
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Copyright © 2013 Elsevier Inc. All rights reserved.

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