T-Cell Differentiation

Nicola Gagliani, Samuel Huber

Enrico Lugli

CD4+ T helper cells orchestrate the immune response and play a pivotal role during infection, chronic inflammatory, autoimmune diseases, and carcinogenesis. CD4+ T helper cells can be subdivided into different subsets, which are characterized by a specific network of transcriptional regulators and unique cytokine profiles: Th17 cells express RORγt that in turn promotes the transcription of Il17a, Il17f; Th1 cells, expresses T-bet and produces IFN-γ, IL-2, and TNF-α; Th2 cells express GATA-3 and secrete IL-4, IL-5, and IL-13. The two most studied regulatory T cell subtypes are Foxp3+ regulatory T cells, which can be generated either in the thymus (tTreg) or induced in peripheral lymphoid organs (pTregs) and type 1 regulatory T cells (Tr1), which are induced in the periphery. These T helper cell subsets can be differentiated from naïve T cells. In addition, recent findings indicate that some T helper cell subsets can emerge from other T helper cells, suggesting a certain degree of plastiticy. Here we report basic aspects of T helper cell differentiation and function while underlining some still open questions.