The development and fate of follicular helper T cells defined by an IL-21 reporter mouse

Nat Immunol. 2012 May;13(5):491-8. doi: 10.1038/ni.2261.

Abstract

Germinal centers require CD4⁺ follicular helper T cells (TFH cells), whose hallmark is expression of the transcriptional repressor Bcl-6, the chemokine receptor CXCR5 and interleukin 21 (IL-21). To track the development and fate of TFH cells, we generated an IL-21 reporter mouse by introducing sequence encoding green fluorescent protein (GFP) into the Il21 locus; these mice had expression of IL-21–GFP in CD4⁺CXCR5⁺PD-1⁺ TFH cells. IL-21–GFP⁺ TFH cells were multifunctional helper cells that coexpressed several cytokines, including interferon-g (IFN-g), IL-2 and IL-4. TFH cells proliferated and gave rise to transferrable memory cells with plasticity, which differentiated after recall into conventional effector helper T cells and TFH cells. Thus, we demonstrated that TFH cells were not terminally differentiated but instead retained the flexibility to be recruited into other helper T cell subsets and nonlymphoid tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology*
  • Cell Proliferation
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Gene Expression
  • Germinal Center / immunology*
  • Germinal Center / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Immunologic Memory / physiology
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-4 / metabolism
  • Interleukins / genetics
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Programmed Cell Death 1 Receptor
  • Receptors, CXCR5 / genetics
  • Receptors, CXCR5 / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism

Substances

  • Antigens, Differentiation
  • CXCR5 protein, mouse
  • Cytokines
  • IL10 protein, mouse
  • Interleukin-2
  • Interleukins
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Receptors, CXCR5
  • Interleukin-10
  • Green Fluorescent Proteins
  • Interleukin-4
  • Interferon-gamma
  • interleukin-21