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

doi:10.1073/pnas.0812681106

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

Departments of ^aMedicine and Microbiology,
^bPediatric Dentistry, and
^cGenetics, University of Alabama at Birmingham, Birmingham, AL 35294

Edited by Robert L. Coffman, Dynavax Technologies, Berkeley, CA, and approved September 24, 2009 (received for review January 8, 2009)

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.

Footnotes

¹To whom correspondence should be addressed. E-mail: ycong{at}uab.edu or coelson{at}uab.edu
Author contributions: Y.C. and C.O.E. designed research; Y.C. and T.F. performed research; K.F. and T.R.S. contributed new reagents/analytic tools; Y.C. and C.O.E. analyzed data; and Y.C. and C.O.E. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0812681106/DCSupplemental.