Affinity for self antigen selects Treg cells with distinct functional properties

Regulatory T cells (Treg cells) have essential roles in maintaining immunohomeostasis. Palmer and colleagues identify two distinct subsets of Treg cells with differing degrees of self-reactivity and regulatory function. The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully understood. We identified two Treg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITRhiPD-1hiCD25hi (Triplehi) Treg cells were highly self-reactive and controlled lympho-proliferation in peripheral lymph nodes. GITRloPD-1loCD25lo (Triplelo) Treg cells were less self-reactive and limited the development of colitis by promoting the conversion of CD4+ Tconv cells into induced Treg cells (iTreg cells). Although Foxp3-deficient (Scurfy) mice lacked Treg cells, they contained Triplehi-like and Triplelo-like CD4+ T cells zsuper> T cells infiltrated the skin, whereas Scurfy TripleloCD4+ 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 Treg cells into distinct subsets with non-overlapping regulatory activities.