Gene expression profiling of WT and STAT3-/- Tc17 CD8+ T cells. Gene expression profiling of WT and STAT3-/- Tc17 CD8+ T cells

CD8+ T cells are pre-programmed for cytotoxic differentiation. However, a subset of effector CD8+ T cells (‘Tc17’) produce IL-17 and fail to express cytotoxic genes. Here, we show that the transcription factors directing IL-17 production inhibit cytotoxicity despite persistent Runx3 expression. Cytotoxic gene repression did not require the transcription factor Thpok. We further show that STAT3 restrained cytotoxic gene expression in CD8+ T cells and that RORgt represses cytotoxic genes by inhibiting the functions but not the expression of the ‘cytotoxic’ transcription factors T-bet and Eomesodermin. Thus, the transcriptional circuitry directing IL-17 expression inhibits cytotoxic functions. Overall design: Naïve WT and Cd4cre+ STAT3fl/fl (STAT3-/-) CD8+ T cells were sorted and mix at 1:1 ratio before activation in the presence of IL-12 (Tc1) or IL-6 and TGFb (Tc17). After 4 days WT and STAT3-/- cells were sorted separetly based on the expression of allelic markers