CD5 Instructs Extrathymic Regulatory T Cell Development in Response to Self and Tolerizing Antigens.
Henderson, Jacob G. 1; Opejin, Adeleye 1; Jones, Andrew 1; Gross, Cindy 1; Hawiger, Daniel 1,*
[Article] Immunity. 42(3):471-483, March 2015.

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: 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 Cd5-/- and CD5lo T cells was inhibited by even small amounts of interleukin-4 (IL-4), IL-6, and interferon-[gamma] (IFN-[gamma]) produced by bystander lymphocytes, while CD5hi T cells resisted this inhibition of Treg cell induction. Our findings further revealed that CD5 promoted 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.

* CD5 promotes Treg cell conversion in response to self and tolerizing peripheral antigens

* CD5 governs Treg cell induction by modifying effector cell-differentiating signals

* CD5 blocks inhibitory effects of PI3K/mTOR activation on Treg cell induction

(C) 2015Elsevier, Inc.