Fig. 1.
The differentiation and regulation of CD4+ T cell subsets. Naive T cells primed by antigen-presenting cells (APC) such as dendritic cells (DC) can differentiate into T regulatory-1 (Tr1)/T helper type 3 (Th3), Th1, Th2 or Th17 cells depending upon the cytokine environment. Priming in the presence of interleukin (IL)-10/transforming growth factor (TGF)-β, IL-12, IL-4 or combinations of IL-6/IL-1/IL-23 promotes the differentiation of Tr1/Th3, Th1, Th2 or Th17 cells, respectively [113]. Th17 cells can be regulated negatively by Th1 or Th2 cells. Tr1 and Th3 cells secrete IL-10 and TGF-β which can suppress effector cell responses, primarily by suppressing APC function. Natural regulatory T cells (Treg) cells are derived from the thymus (although they may also be converted in the periphery) and can suppress effector T cell responses directly or via the APC [72].