Effector γδ t cell differentiation relies on master but not auxiliary th cell transcription factors

γδ T lymphocytes are programmed into distinct IFN-γ-producing CD27+ (gd27+) and IL-17-producing CD272 (γδ272) subsets that play key roles in protective or pathogenic immune responses. Although the signature cytokines are shared with their ab Th1 (for γδ27+) and Th17 (for γδ272) cell counterparts, we dissect in this study similarities and differences in the transcriptional requirements of murine effector γδ27+, γδ272CCR62, and γδ272CCR6+ γδ T cell subsets and ab T cells. We found they share dependence on the master transcription factors T-bet and RORgt for IFN-γ and IL-17 production, respectively. However, Eomes is fully dispensable for IFN-γ production by gd T cells. Furthermore, the Th17 cell auxiliary transcription factors RORa and BATF are not required for IL-17 production by γδ272 cell subsets. We also show that gd272 (but not γδ27+) cells become polyfunctional upon IL-1b plus IL-23 stimulation, cosecreting IL-17A, IL-17F, IL-22, GM-CSF, and IFN-γ. Collectively, our in vitro and in vivo data firmly establish the molecular segregation between γδ27+ and γδ272 T cell subsets and provide novel insight on the nonoverlapping transcriptional networks that control the differentiation of effector gd versus ab T cell subsets.