The activation of self-antigen specific T cell repertoire during acute tissue injury.

Abstract

Abstract Self-antigen specific T cells are prevalent in the mature adaptive immune repertoire. At steady state, these self-antigen specific T cells appear to be regulated through a combination of central and peripheral mechanisms of tolerance. Understanding how these self-antigen specific T cells escape tolerance to mediate autoimmune disease remains of significant scientific and clinical interest. Importantly, the mechanisms that determine whether the self-reactivity will exacerbate or regulate the ongoing immune response are unknown. Utilizing an experimental animal model where mice express a complex of three model T cell epitopes (2W, gp66, and OVA) in a tissue restricted manner, we identified and tracked the activation of endogenous polyclonal T cells that recognize these transgenic epitopes as self-antigens. Interestingly, in the context of acute injury to lung tissue of mice expressing the epitopes in the alveolar epithelium, we detect an asymmetric expansion of the self-antigen specific regulatory T cell (Treg) compartment while the conventional T cell populations remained static. These findings suggest that the self-antigen specific T cell repertoire is uniquely programmed to generate a protective response to acute tissue injury.