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

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 celldeficient 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.

Systemic Flagellin Immunization Stimulates Mucosal CD103+ Dendritic Cells and Drives Foxp3+ Regulatory T Cell and IgA Responses in the Mesenteric Lymph Node

“…On the basis of this and other studies (51,52), it is reasonable to suggest that the parallel development of Ag-specific IgA and Treg responses is related to the recruitment of CD103 + DCs to the MLN. Previous work has identified links between Tregs, Treg function, Treg differentiation, and IgA switching (53). One issue that will need to be addressed in greater detail is the relationship between Treg and T follicular helper cells in regulating switching to IgA.…”

“…One issue that will need to be addressed in greater detail is the relationship between Treg and T follicular helper cells in regulating switching to IgA. Although Treg responses in GCs have been shown to aid the specificity of the response and reduce the risk of autoimmunity (54), it is also likely that they can contribute to the magnitude of the switched response to IgA (50)(51)(52)(53).…”

Re-thinking the functions of IgA+plasma cells

“…On the other hand, PP and MLN can support both TD as well as TI IgA induction. [27][28][29] Several CD4 C T cell subsets have been implicated in germinal center (GC)-driven IgA responses including T-regulatory cells (Treg), 30 T-follicular helper cells (T FH ) 31 and Th17 cells. 32,33 It is likely that the generation of IgA C PC depends on the nature of the Ag and the location of where B cells are primed.…”

Helicobacter pylori infection in patients with selective immunoglobulin a deficiency

“…Importantly, it has to be mentioned that IgA production is regulated by regulatory T cells (T reg ) in an antigen-specific manner [33]. Thus, disturbances in the T reg -IgA axis might play an important role in the pathophysiology of H. pylori infection in IgAD patients.…”