A Dominant, Coordinated T Regulatory Cell-IgA Response to the Intestinal Microbiota

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.