Herpesvirus entry mediator (HVEM), a TNF receptor superfamily member, has been previously described as a T cell costimulatory receptor. Surprisingly, HVEM–/– T cells showed enhanced responses to in vitro concanavalin A (ConA) stimulation when compared with WT T cells. Consistent with these findings, HVEM–/– mice exhibited increased morbidity and mortality as compared with WT mice in a model of ConA-mediated T cell–dependent autoimmune hepatitis. HVEM–/– mice produced higher levels of multiple cytokines, which were dependent on the presence of CD4+ T cells. Furthermore, HVEM–/– mice were more susceptible to MOG peptide–induced experimental autoimmune encephalopathy, and they showed increased T cell proliferation and cytokine production in response to antigen-specific challenge. Taken together, our data revealed an unexpected regulatory role of HVEM in T cell–mediated immune responses and autoimmune diseases.
Yang Wang, Sumit K. Subudhi, Robert A. Anders, James Lo, Yonglian Sun, Sarah Blink, Yugang Wang, Jing Wang, Xiaojuan Liu, Karin Mink, Daniel Degrandi, Klaus Pfeffer, Yang-Xin Fu
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