Human CD8 + T cells display a differential ability to undergo cytokine-driven bystander activation

► Peripheral blood mononuclear cells from individual donors secreted varying amounts of IL-12 after L. monocytogenes infection. ► Human CD8 + T cells from different blood donors varied in their innate responsiveness to stimulation with IL-12 plus IL-18. ► CD8 + T cells from a subset of donors (12.5%) failed to rapidly secrete IFNγ. ► The magnitude of the rapid IFNγ response correlated with intrinsic T cell responsiveness, not the amount of IL-12 produced. A subset of CD44 hiCD8 + T cells in some, but not all mice, can be induced to rapidly secrete IFNγ during infection with Listeria monocytogenes. This response is dependent on the presence of both IL-12 and IL-18 and does not require engagement of the T cell receptor. In this study, we demonstrate that human CD8 + T cells also vary widely in their ability to secrete IFNγ within 15 h of either Listeria infection or cytokine stimulation. The magnitude of the rapid IFNγ response correlated more closely with the intrinsic responsiveness of the T cells to cytokine stimulation rather than the amount of IL-12 produced. CD8 + T cells from 2 out of 16 blood donors (12.5%) failed to generate a significant IFNγ response. These results demonstrate that bystander activation of CD8 + T cells varies among individuals and validate further study of the differential responses observed using BALB/c vs. C57BL/6 mice.