A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota

Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19256-61. doi: 10.1073/pnas.0812681106. Epub 2009 Nov 4.

Abstract

A T cell receptor transgenic mouse line reactive to a microbiota flagellin, CBir1, was used to define mechanisms of host microbiota homeostasis. Intestinal IgA, but not serum IgA, was found to block mucosal flagellin uptake and systemic T cell activation in mice. Depletion of CD4(+)CD25(+) Tregs decreased IgA(+) B cells, total IgA, and CBir1-specific IgA in gut within days. Repletion of T cell-deficient mice with either CD4(+)CD25(+) or CD4(+)foxp3(+) Tregs restored intestinal IgA to a much greater extent than their reciprocal CD4(+) subsets, indicating that Tregs are the major helper cells for IgA responses to microbiota antigens such as flagellin. We propose that the major role of this coordinated Treg-IgA response is to maintain commensalism with the microbiota.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology*
  • B-Lymphocytes / immunology
  • Flagellin / immunology*
  • Forkhead Transcription Factors / immunology
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin A / immunology*
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Intestines / immunology
  • Intestines / microbiology*
  • Lymphocyte Depletion
  • Mice
  • Mice, Transgenic
  • Mucous Membrane / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Antigens, Bacterial
  • CBir1 flagellin
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Immunoglobulin A
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Antigen, T-Cell, alpha-beta
  • Flagellin