Circulating precursor CCR7(lo)PD-1(hi) CXCR5⁺ CD4⁺ T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure

Immunity. 2013 Oct 17;39(4):770-81. doi: 10.1016/j.immuni.2013.09.007.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology*
  • Antigens / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • B-Lymphocytes / virology
  • Cell Differentiation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Gene Expression
  • Germinal Center / immunology
  • Germinal Center / pathology
  • Germinal Center / virology
  • Humans
  • Immunity, Humoral
  • Immunologic Memory*
  • Immunophenotyping
  • Inducible T-Cell Co-Stimulator Protein / genetics
  • Inducible T-Cell Co-Stimulator Protein / immunology
  • Mice
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / immunology*
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, CXCR / genetics
  • Receptors, CXCR / immunology*
  • Receptors, CXCR5 / genetics
  • Receptors, CXCR5 / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / pathology
  • T-Lymphocytes, Helper-Inducer / virology

Substances

  • ACKR3 protein, human
  • Antibodies
  • Antigens
  • BCL6 protein, human
  • CXCR5 protein, human
  • DNA-Binding Proteins
  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Protein
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, CXCR
  • Receptors, CXCR5