Secretion of IL-12, in synergy with IL-18, leads to the generation of Th1 cells. Initial IL-12 production directs the upregulation of IL-18R and IL-12Rβ2 expression on the surface of Th1 precursor (Th1p) cells that allows IL-18 to aid IL-12 in Th1 polarization. TGF-β secretion can polarize naive cells toward a regulatory phenotype or an autoaggressive phenotype, depending on the cytokine environment: secretion of TGF-β alone by APCs supports Treg formation (which counteracts autoimmune inflammation) from Treg precursor cells (Treg-p cells). However, the additional presence of IL-6 results in the production of Th17 cells, which are now considered to be the pathogenic T cell population during autoimmunity. The pathogenic, APC-derived cytokine IL-23 is critical for the maintenance and survival of these autoreactive Th17 cells. The interaction of APCs and Th2 precursor (Th2p) cells in the absence of IL-12 and IL-18 induces the production of the Th2 cytokine IL-4 by T cells, which acts in an autocrine fashion to polarize committed Th2 cells.