| Self-reactive T cells can escape thymic deletion and therefore some of these potentially autoaggressive T cells need to convert into regulatory T (Treg) cells to help control responses against self. However, it remains unknown how peripheral self-reactive T cells are specifically instructed to become Treg cells. We report that CD5, whose expression is upregulated in T cells by self and tolerizing antigens in the thymus and periphery, governed extrathymic Treg cell development. CD5 modified effector cell-differentiating signals that inhibit Treg cell induction. Treg cell conversion of T cells with deletion of the CD5 gene or low expression of CD5 protein was inhibited by even small amounts of interleukin-4, interleukin-6, and interferon-gamma produced by bystander lymphocytes, while those cells with high expression of CD5 resisted this inhibition of Treg cell induction. Our findings further revealed that CD5 inhibited Treg cell induction by blocking mechanistic target of rapamycin (mTOR) activation. Therefore CD5 instructs extrathymic Treg cell development in response to self and tolerizing antigens. |
