CD4⁺ T-cell effector subsets. Antigen-specific stimulation of naive CD4⁺ T cells in the presence of certain cytokines induces expression of lineage-specific transcription factors, resulting in differentiation into CD4⁺ T-cell effector subsets. IFN-γ and IL-12 lead to the expression of T-bet, resulting in Th1 cell differentiation. CD4⁺ T-cell activation in the presence of IL-4 results in Th2 cell development mediated by GATA3; however, the addition of TGF-β causes differentiation into Th9 cells. The combination of IL-6 and TGF-β is necessary for RORγt expression, resulting in Th17 cell development, whereas the presence of IL-6 alone or with other unknown cytokines possibly results in Th22 cell differentiation by expression of AHR. Finally, IL-21 appears to be important for the development of Tfh cells through induction of Bcl-6.