There is growing evidence from mouse studies that IL-17 producing CD4 T cells play a key role in various chronic inflammatory conditions. However IL-17 producing cells were also shown to have a protective role in different models of infections through recruitment of neutrophils in early phases of the immune response. Despite the critical role described for TH17 cells in infection and autoimmunity, their identification in humans remains elusive. Surface markers that precisely identify human TH17 cells are instrumental to study their physiology and repertoire and might represent a therapeutic target for IL-17 mediated diseases. We report that memory and effector IL-17 producing CD4+ T cells both in peripheral blood and in inflamed sinovial fluid are present within a subset of CCR6+ cells. Bona fide TH17 cells, capable of producing IL-17 but no IFN-g, expressed CCR6 and CCR4, whereas cells capable of producing both IL-17 and IFN-g expressed CCR6 and CXCR3. The IL-17 producing phenotype was stable upon in vitro expansion and was associated with expression of RORgt. Moreover, the same correlation between chemokine receptors and cytokine production was also observed on IL-17 producing T cells differentiated in vitro from naive CD4+ T cells. Interestingly memory T cells specific for Candida albicans were mostly present in the CCR6+CCR4+ subset and released IL-17, while cells specific Mycobacterium tubercolosis were distributed exclusively in the CCR6+CXCR3+ subset and released high levels og IFN-g. Taken together these results identify a combination of surface markers that allow precise identification and characterization of TH17 cells and suggest that TH17 have distinctive migratory capacity.
