Affinity for self antigen selects Treg cells with distinct functional properties

Regulatory T cells (T reg cells) have essential roles in maintaining immunohomeostasis. Palmer and colleagues identify two distinct subsets of T reg cells with differing degrees of self-reactivity and regulatory function. The manner in which regulatory T cells (T reg cells) control lymphocyte homeostasis is not fully understood. We identified two T reg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITR hi PD-1 hi CD25 hi (Triple hi ) T reg cells were highly self-reactive and controlled lympho-proliferation in peripheral lymph nodes. GITR lo PD-1 lo CD25 lo (Triple lo ) T reg cells were less self-reactive and limited the development of colitis by promoting the conversion of CD4 + T conv cells into induced T reg cells (iT reg cells). Although Foxp3-deficient (Scurfy) mice lacked T reg cells, they contained Triple hi -like and Triple lo -like CD4 + T cells zsuper> T cells infiltrated the skin, whereas Scurfy Triple lo CD4 + T cells induced colitis and wasting disease. These findings indicate that the affinity of the T cell antigen receptor for self antigen drives the differentiation of T reg cells into distinct subsets with non-overlapping regulatory activities.