T-follicular helper cells survive as long-term memory cells

Eur J Immunol. 2012 Aug;42(8):1981-8. doi: 10.1002/eji.201242540.

Abstract

T-follicular helper (TFH) cells represent the subpopulation of CD4(+) T cells that provides help for antigen-specific B cells in the GC response. They are generated from naïve T cells during an immune response and are imprinted by their master transcription factor Bcl-6. It has been a long-standing question if TFH cells contribute to the CD4(+) memory pool after the GC response has been terminated. To answer this question, we sorted antigen-specific TFH and non-TFH effector cells from an ongoing GC response and transferred them into naïve mice. Without further signals via the TCR, transferred cells rapidly contracted with a small population of both TFH and non-TFH cells surviving as memory cells in peripheral lymphoid organs for at least 4 weeks in the absence of antigen. TFH cells strongly downregulated their signature genes Bcl-6, CXCR5, and PD-1 in the memory phase. Upon rechallenge with antigen they rapidly upregulated these markers again. An enhanced potential to produce IL-21, paired with higher expression of CXCR5 and lower expression of CCR7, should enable TFH memory cells to provide more efficient help for antigen-specific B cells than their non-TFH counterparts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Differentiation / biosynthesis*
  • Antigens, Differentiation / immunology
  • Cell Differentiation
  • Down-Regulation
  • Germinal Center / immunology
  • Immunologic Memory*
  • Interleukin-21
  • Interleukins / biosynthesis
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Programmed Cell Death 1 Receptor
  • Proto-Oncogene Proteins c-bcl-6 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-6 / immunology
  • Receptors, CCR7 / biosynthesis
  • Receptors, CXCR5 / biosynthesis*
  • Receptors, CXCR5 / immunology
  • Spleen / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Up-Regulation

Substances

  • Antigens, Differentiation
  • CXCR5 protein, mouse
  • Ccr7 protein, mouse
  • Interleukins
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, CCR7
  • Receptors, CXCR5
  • Interleukin-21