The role of self-reactivity in regulatory T cell development and acquisition of diverse regulatory activities

The importance of regulatory T cells (Tregs) in maintaining lymphocyte homeostasis is best appreciated in mice and humans lacking these cells. FoxP3 KO (scurfy) mice and patients with immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome suffer from excessive lymphocyte activation, lymphocytic infiltration into peripheral organs, and colitis leading to death at an early age. In healthy mice and humans, Tregs control homeostatic proliferation of conventional T and B cells and prevent colitis. Tregs have been classified based on their activation status, expression of surface markers and their ability to migrate to certain tissues. In humans, the proportion of activated and resting Tregs vary with age and the presence immunological disorders. While Tregs have been shown to express self-reactive and foreign-antigen reactive T cell receptors (TCRs), it’s not clear how their antigen specificity determines their regulatory function.
In this study, we identified two Treg cell populations, which are differentially selected, based on their affinity for self-antigens; we further investigate their self- reactivity in vitro and assessed their different regulatory properties using three disease models in vivo.