More detailed information stems from mouse studies, in which TGF-β and IL-6 have been used to drive IL-17+ CD8+ T cell differentiation from CD8+ T cells , , , , , , , leading to frequencies ranging from 19%–64% (Table 1). TGF-β decreases IFN-γ production, while reducing cytolytic activity and expression of the cytolytic marker granzyme B within in vitro cultured CD8+ T cells , . TGF-β also inhibits CD8+ T cell proliferation and division, but in concert with IL-6, these TGF-β-mediated actions are opposed while maintaining reduced cytolytic activity, a characteristic of IL-17+ CD8+ T cells . A role for IL-6 in IL-17+ CD8+ T cell induction was also shown in mice in vivo, since after allogeneic stem cell transplantation IL-6R blockade reduced IL-17+ CD8+ T cell frequencies . In contrast to IL-6, the effects of TGF-β may vary between in vitro and in vivo conditions. TGF-β removal from the IL-17+ CD8+ T cell differentiation cocktail containing IL-1β, IL-2, IL-6, IL-21, IL-23, α-IL-4 and α-IFN-γ mAbs led to a strong reduction in IL-17+ CD8+ T cell percentages in vitro . However, in vivo TGF-β neutralisation in mice did not considerably affect IL-17+ CD8+ T cell frequencies . Furthermore, TGF-βRIIDN mice with impaired TGF-β signalling still exhibited IL-17+ CD8+ T cell differentiation, whilst IL-17+ CD4+ T cell differentiation was inhibited , suggesting that TGF-β may not be critical for in vivo IL-17+ CD8+ T cell differentiation, and that cytokines required for IL-17 induction in CD4+ versus CD8+ T cells may differ.