CD160 Stimulates CD8+ T Cell Responses and Is Required for Optimal Protective Immunity to Listeria monocytogenes

CD160 promotes NK cell cytotoxicity and IFN-γ production, but the function of CD160 on CD8 + T cells remains unclear with some studies supporting a coinhibitory role and others a costimulatory role. In this study, we demonstrate that CD160 has a costimulatory role in promoting CD8 + T cell effector functions needed for optimal clearance of oral Listeria monocytogenes infection. CD160 −/− mice did not clear oral L. monocytogenes as efficiently as wild type (WT) littermates. WT RAG −/− and CD160 −/− RAG −/− mice similarly cleared L. monocytogenes , indicating that CD160 on NK cells does not contribute to impaired L. monocytogenes clearance. Defective L. monocytogenes clearance is due to compromised intraepithelial lymphocytes and CD8 + T cell functions. There was a reduction in the frequencies of granzyme B–expressing intraepithelial lymphocytes in L. monocytogenes –infected CD160 −/− mice as compared with WT littermate controls. Similarly, the frequencies of granzyme B–expressing splenic CD8 + T cells and IFN-γ and TNF-α double-producer CD8 + T cells were significantly reduced in L. monocytogenes –infected CD160 −/− mice compared with WT littermates. Adoptive transfer studies showed that RAG −/− recipients receiving CD160 −/− CD8 + T cells had a higher mortality, exhibited more weight loss, and had a higher bacterial burden compared with RAG −/− recipients receiving WT CD8 + T cells. These findings demonstrate that CD160 provides costimulatory signals to CD8 + T cells needed for optimal CD8 + T cell responses and protective immunity during an acute mucosal bacterial infection.