Dissecting CD8+ NKT Cell Responses to Listeria Infection Reveals a Component of Innate Resistance

A small pool of NK1.1(+) CD8(+) T cells is harbored among the conventional CD8(+) T cell compartment. Conclusions drawn from the analysis of immune responses mediated by cytotoxic CD8(+) T cells are often based on the total population, which includes these contaminating NK1.1(+) CD8(+) T cells. An unresolved question is whether NK1.1(+) CD8(+) cells are conventional T cells that acquire NK1.1 expression upon activation or delineation into memory phenotype or whether they are a distinct cell population that induces immune responses in a different manner than conventional T cells. To address this question, we used the Listeria monocytogenes model of infection and followed CD8(+) NK1.1(+) T cells and NK1.1(-) CD8(+) T cells during each phase of the immune response: innate, effector, and memory. Our central finding is that CD8(+) NK1.1(+) cells and conventional NK1.1(-) CD8(+) T cells both contribute to the adaptive immune response to Listeria, but only CD8(+) NK1.1(+) cells were equipped with the ability to provide a rapid innate immune response, as demonstrated by early and Ag-independent IFN-γ production, granzyme B expression, and degranulation. More importantly, purified conventional CD8(+) T cells alone, in the absence of any contaminating CD8(+) NK1.1(+) cells, were not sufficient to provide early protection to lethally infected mice. These results highlight the role of CD8(+) NK1.1(+) T cells in mounting early innate responses that are important for host defense and support the therapeutic potential of this subset to improve the effectiveness of protective immunity.