The non-classical CD8+ T cell response to murine cytomegalovirus

Abstract

Abstract There is a growing interest in the role of MHC class Ib-restricted CD8+ T cells, referred to as non-classical T cells, such as MAIT cells and NKT cells. Non-classical CD8+ T cells have been shown to participate during the immune response towards a number of bacterial and viral pathogens. However, the overall role of these cells remains largely undetermined. We sought to investigate their contribution during murine cytomegalovirus (MCMV) infection, a well-established model for human cytomegalovirus. To circumvent the known role of conventional CD8+ T cells we utilize KbDb−/− mice, which lack MHC class Ia molecules. Following MCMV challenge, a subset of non-classical CD8+ T cells undergoes robust expansion, gains effector functions, and subsequently contracts. Interestingly, there is a prolonged inflammatory phenotype not observed in B6 or β2m−/− control animals. Non-classical CD8+ T cells from long-term infected KbDb−/− mice are also capable of robust proliferation in response to secondary MCMV infection, indicating that these T cells exhibit a memory phenotype. Using RAGKbDb−/− animals, we determined that adoptively transferred non-classical CD8+ T cells are sufficient to protect against MCMV-induced lethality. The population we describe is more phenotypically similar to conventional CD8+ T cells than innate non-classical T cells. Altogether, our data indicate that MHC class Ib-restricted CD8+ T cells may substitute for conventional CD8+ T cells when their functions are compromised during CMV immunoevasion.