Contribution of CD8⁺ T cells to innate immunity: IFN-γ secretion induced by IL-12 and IL-18

The role of CD8⁺ T cells in adaptive immunity is well documented and involves numerous effector mechanisms including direct cytolysis of targets and secretion of cytokines. The role of CD8⁺ T cells in innate immunity has not been previously appreciated. Using J774 macrophages infected in vitro with the intracellular bacterium, Listeria monocytogenes (LM), we show that CD8⁺ T cells isolated from naïve C57BL/6 (B6) mice respond rapidly by secreting IFN-γ. CD8⁺ T cells secreting IFN-γ can also be found in naïve B6 mice 16 h after infection with LM. This rapid IFN-γ response is TCR-independent and mediated through the actions of IL-12 and IL-18. Cell surface staining and cell sorting experiments indicate that these novel CD8⁺ T cells express memory markers. In vitro CFSE-labeling experiments show that IFN-γ-secreting CD8⁺ T cells proliferate rapidly after 2 days in culture and after 4 days constitute the majority of the CD8⁺ T cell population. Together, these data suggest an important role for IFN-γ-secreting CD8⁺ T cells in the innate response to bacterial pathogens.