Lung injury induces preferential expansion of Foxp3 +regulatory T cells over conventional T cells in self-antigen specific CD4 +T cell repertoire.

Abstract

Abstract Self antigen-specific T cells are prevalent in the mature adaptive immune repertoire. At steady state, these T cells are regulated by various mechanisms of peripheral tolerance. Characterizing the activation of these self antigen-specific T cells during inflammation may shed crucial insights into the pathogenesis of autoimmunity. Utilizing an experimental animal model where mice express three model T cell epitopes (2W, gp66, and OVA) in a tissue restricted manner, we detect the exclusive expansion of autoreactive regulatory T cells (Tregs) following acute lung injury that is dependent on recognition of their cognate self antigen and IL-2 signaling. Conversely, conventional T cells of the same self antigen-specificity did not expand during inflammation, even following the depletion of endogenous Tregs. Therefore, our findings suggest that the self-antigen specific T cell repertoire may serve a regulatory function during acute tissue damage to regulate the ongoing immune response and limit the possibility of autoimmunity.