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Effector T Cell Differentiation Relies on Master but Not Auxiliary Th Cell Transcription Factors.

Barros-Martins, J;Schmolka, N;Fontinha, D;Pires de Miranda, M;Simas, JP;Brok, I;Ferreira, C;Veldhoen, M;Silva-Santos, B;Serre, K;

T lymphocytes are programmed into distinct IFN–producing CD27(+) (27(+)) and IL-17-producing CD27(-) (27(-)) subsets that play key roles in protective or pathogenic immune responses. Although the signature cytokines are shared with their Th1 (for 27(+)) and Th17 (for 27(-)) cell counterparts, we dissect in this study similarities and differences in the transcriptional requirements of murine effector 27(+), 27(-)CCR6(-), and 27(-)CCR6(+) T cell subsets and T cells. We found they share dependence on the master transcription factors T-bet and RORt for IFN- and IL-17 production, respectively. However, Eomes is fully dispensable for IFN- production by T cells. Furthermore, the Th17 cell auxiliary transcription factors ROR and BATF are not required for IL-17 production by 27(-) cell subsets. We also show that 27(-) (but not 27(+)) cells become polyfunctional upon IL-1 plus IL-23 stimulation, cosecreting IL-17A, IL-17F, IL-22, GM-CSF, and IFN-. Collectively, our in vitro and in vivo data firmly establish the molecular segregation between 27(+) and 27(-) T cell subsets and provide novel insight on the nonoverlapping transcriptional networks that control the differentiation of effector versus T cell subsets.