Th17: the third member of the effector T cell trilogy

T helper responses have now grown to include three T cell subsets: Th1, Th2 and Th17. Th17 cells have recently emerged as a third independent T cell subset that may play an essential role in protection against certain extracellular pathogens. However, Th17 cells with specificity for self-antigens are highly pathogenic and lead to the development of inflammation and severe autoimmunity. A combination of TGF-beta plus IL-6 and the transcription factors STAT3 and ROR gamma t were recently described to be essential for initial differentiation of Th17 cells and IL-23 for the later stabilization of the Th17 cell subset. Here, we introduce another player IL-21 produced by Th17 themselves, which plays an important role in the amplification of Th17 cells. Thus, Th17 cells may undergo three distinct steps of development: differentiation, amplification and stabilization in which distinct cytokines play a role.