Effector gd T Cell Differentiation Relies on Master but Not Auxiliary Th Cell Transcription Factors
gd T lymphocytes are programmed into distinct IFN g producing CD27+ (gd27+ and IL 17 producing CD27 (gd27 subsets that play key roles in protective or pathogenic immune responses. Although the signature cytokines are shared with their ab Th1 (for gd27+ and Th17 (for gd27 cell counterparts, we dissect in this study similarities and differences in the transcriptional requirements of murine effector gd27+ gd27 CCR6 and gd27 CCR6+ gd T cell subsets and ab T cells. We found they share dependence on the master transcription factors T bet and RORgt for IFN g and IL 17 production, respectively. However, Eomes is fully dispensable for IFN g production by gd T cells. Furthermore, the Th17 cell auxiliary transcription factors RORa and BATF are not required for IL 17 production by gd27 cell subsets. We also show that gd27 (but not gd27+ cells become polyfunctional upon IL 1b plus IL 23 stimulation, cosecreting IL 17A, IL 17F, IL 22, GM CSF, and IFN g. Collectively, our in vitro and in vivo data firmly establish the molecular segregation between gd27+ and gd27 T cell subsets and provide novel insight on the nonoverlapping transcriptional networks that control the differentiation of effector gd versus ab T cell subsets.
The Journal of Immunology