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.
(Copyright © 2018 The Authors.)