Cutting edge:: IL-12 inversely regulates T-bet and eomesodermin expression during pathogen-induced CD8+ T cell differentiation

Cytokines are critical determinants for specification of lineage-defining transcription factors of CD4(+) T cell subsets. Little is known, however, about how cytokines regulate expression of T-bet and eomesodermin (Eomes) in effector and memory CD8(+) T cells. We now report that IL-12, a signature of cell-mediated immunity, represses Eomes while positively regulating T-bet in effector CD8(+) T cells during infection with Listeria monocytogenes. After resolution of infection and abatement of IL-12 signaling, Eomes expression rises whereas T-bet expression declines in memory CD8(+) T cells. Eomes becomes derepressed in effector cells by ablation of IL-12 signaling. In the absence of IL-12, the dynamics of clonal expansion and contraction are also perturbed. Together, these results reveal how a pathogen-associated signal such as IL-12, could act, as. a switch, regulating appropriate clonal growth and decline while, in parallel shaping a unique pattern of fate-determining transcription factors. The Journal of Immunology, 2006, 177: 7515-7519.