Salivary gland lymphocyte response to murine cytomegalovirus (INC1P.344)

Abstract The β-herpes virus MCMV, a homologue of HCMV, is a well-characterized animal model of viral infection that results in a non-replicative, chronic infection of an immune-competent animal. In most organs, MCMV is cleared within days by cytotoxic lymphocytes. However, the virus persists in the submandibular salivary glands (SMG) for several weeks, before establishing latency for the life of the host. NK cells are crucial for the early containment of MCMV before T cells can mount an effector response. Recent work from our laboratory has shown that SMG NK cells are hyporesponsive during MCMV infection. Here we show that SMG NK cells regain normal effector functions against MCMV when adoptively transferred into different tissue environments. This indicates that the hyporesponsive phenotype observed is tissue specific, and not cell-intrinsic. In addition, using E4BP4 deficient animals, we determined that two CD3-NK1.1+ subsets reside within the salivary glands. One subset is derived from the conventional NK cell population and relies on E4BP4 for development, while the other is E4BP4 independent. When the E4BP4 independent NK cells are transferred into different tissue environments, they produce IFN-γ in response to MCMV infection. The SMGs of E4BP4-/- mice also contain a novel population of CD3+NK1.1+NKp46+ cells that produce IFN-γ during MCMV infection. Altogether, our data show that the SMG tissue environment shapes a unique repertoire of NK1.1+ cells with distinctive phenotypes.