FoxP3+ regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability

Nat Commun. 2014 Mar 17;5:3495. doi: 10.1038/ncomms4495.

Abstract

Here, we test the role of FoxP3(+) regulatory T cells (Tregs) in controlling T follicular helper (Tfh) and germinal centre (GC) B-cell responses to influenza. In contrast to the idea that Tregs suppress T-cell responses, we find that Treg depletion severely reduces the Tfh cell response to influenza virus. Furthermore, Treg depletion prevents the accumulation of influenza-specific GCs. These effects are not due to alterations in TGFβ availability or a precursor-progeny relationship between Tregs and Tfh cells, but are instead mediated by increased availability of IL-2, which suppresses the differentiation of Tfh cells and as a consequence, compromises the GC B response. Thus, Tregs promote influenza-specific GC responses by preventing excessive IL-2 signalling, which suppresses Tfh cell differentiation.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Cell Differentiation
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology*
  • Humans
  • Influenza, Human / genetics
  • Influenza, Human / immunology*
  • Interleukin-2 / immunology*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Orthomyxoviridae / immunology
  • Species Specificity
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2