Circulating Precursor CCR7loPD-1hi CXCR5+ CD4+ T Cells Indicate Tfh Cell Activity and Promote Antibody Responses upon Antigen Reexposure
Copyright policy )Circulating Precursor CCR7loPD-1hi 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.
- Monash University Australia
- National Institute of Health Pakistan
- University of Queensland Australia
- UNSW Sydney Australia
- Chinese Academy of Science China (People's Republic of)
Central Memory, Expansion, Receptors, CXCR5, 570, Immunology, Programmed Cell Death 1 Receptor, Generation, T cells, Gene Expression, Cxc Chemokine Receptor-5, CXCR5+ CD4+ T cells, Bcl6 Expression, Antibodies, Interleukin-21, Immunophenotyping, memory, Inducible T-Cell Co-Stimulator Protein, early, Mice, antibody, CCR7loPD-1hi CXCR5+ CD4+ T cells, Immunology and Allergy, Animals, Humans, Antigens, Receptors, CXCR, 2403 Immunology, B-Lymphocytes, Cell Differentiation, 2725 Infectious Diseases, T-Lymphocytes, Helper-Inducer, Germinal Center, Immunity, Humoral, DNA-Binding Proteins, immunological, Infectious Diseases, Follicular Helper-Cell, Differentiation, Effector, 2723 Immunology and Allergy, Proto-Oncogene Proteins c-bcl-6, Center B-Cell, Immunologic Memory
Central Memory, Expansion, Receptors, CXCR5, 570, Immunology, Programmed Cell Death 1 Receptor, Generation, T cells, Gene Expression, Cxc Chemokine Receptor-5, CXCR5+ CD4+ T cells, Bcl6 Expression, Antibodies, Interleukin-21, Immunophenotyping, memory, Inducible T-Cell Co-Stimulator Protein, early, Mice, antibody, CCR7loPD-1hi CXCR5+ CD4+ T cells, Immunology and Allergy, Animals, Humans, Antigens, Receptors, CXCR, 2403 Immunology, B-Lymphocytes, Cell Differentiation, 2725 Infectious Diseases, T-Lymphocytes, Helper-Inducer, Germinal Center, Immunity, Humoral, DNA-Binding Proteins, immunological, Infectious Diseases, Follicular Helper-Cell, Differentiation, Effector, 2723 Immunology and Allergy, Proto-Oncogene Proteins c-bcl-6, Center B-Cell, Immunologic Memory
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