IL-17-producing CD8 + T cells differ in phenotype, metabolic profile and cytokine production to their CD4 + Th17 counterparts

Abstract Th17 cells (CD4+ T cells producing IL-17) are important for clearance of fungal infections and play a critical role in the development and exacerbation of numerous autoimmune diseases. Their differentiation, signalling pathways, cytokine production and metabolism are now well-characterised. As well as CD4+ T cells, CD8+ cells also produce IL-17 family members, and these have been named Tc17 cells. However, much less is known about their development, signalling or metabolism compared to their CD4+ counterparts. Here, we performed a series of in vitro and in vivo analyses of Tc17 cells as well as computational analysis of the published Tabula muris dataset, comparing Tc17 to IL-17− CD8+ T cells and to Th17 cells. We show that murine Tc17 cells are generated in the presence of TGF-β and IL-6, and that cells produced by these culture conditions substantially reflect Tc17 cells seen in vivo; that is, with high expression of PD1, CD6, ICOS and CD161. Tc17 cells show phenotypic and functional differences to their Th17 counterparts, with increased production of IL-2 and IL-22 as well as an increased tendency to produce IL-17F as well as IL-17A. They show a more glycolytic profile than Th17 cells, with lowered mitochondrial membrane potential. This divergent phenotype and cytokine production suggests differential roles in vivo for these two cells. Competing Interest Statement The authors have declared no competing interest.