Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells.

CD4+ T helper 1 (T(H)1) and T(H)2 cells have long been regarded as two sides of a coin in terms of adaptive immune responses. However, as I discuss here, this concept needs to be reconsidered. In particular, recent data indicate that interleukin-17 (IL-17) is produced by T(H) cells that are distinct from the traditional T(H)1- and T(H)2-cell subsets. Furthermore, the generation of these IL-17-producing CD4+ T cells from naive precursors during immune responses is not dependent on the cytokines and transcription factors that mediate T(H)1- and T(H)2-cell development. Given that IL-17 has crucial roles in regulating tissue inflammation and the development of disease in several animal models of autoimmunity, I propose that IL-17-producing CD4+ T cells represent a distinct inflammatory T(H)-cell lineage.