Model for Th cell differentiation from naive CD4+ T cells. In
the presence of IL-12, differentiation of naive CD4+ T cells
into Th1 cells requires activation of the master regulator transcription
factor T-bet through STAT1 and STAT4. Th1 cells produce IFN-γ and are
involved in cell-mediated immunity against intracellular bacteria and
viruses. IL-4 promotes the activation of STAT6 and GATA3, which are
responsible for Th2 cell differentiation. Th2 cells are important in humoral
immunity against parasites, an action that is mediated through their
production of IL-4, IL-5 and IL-13. The combination of TGF-β and
proinflammatory cytokines, such as IL-6 and IL-23, drives the
differentiation of naive CD4+ T cells into IL-17-producing
Th cells (Th17) through the regulation of STAT3 and RORγt. Th17 cells
play a critical role in host protection against extracellular pathogens and
in inflammatory autoimmune diseases. In addition, TGF-β can induce
differentiation of naive CD4+ T cells into
Foxp3+ Treg cells, which produce TGF-β and IL-10 and
act as modulators of immune responses. APC, antigen-presenting cell;
Foxp3+, forkhead box p3+; IFN,
interferon; MHC–TCR, major histocompatibility complex–T-cell
receptor; ROR, retinoid-related orphan receptor; TGF, transforming growth
factor; Th, T helper; Treg, regulatory T.