Human Th17 cells (LL1-7)

Studies in mice have initially suggested that Th17 cells are the pathogenic cells in autoimmune disorders, whereas Th1 cells may behave rather as protective. Subsequent studies in humans have demonstrated the existence of Th cells able to produce both IL-17 and IFN-gamma (Th17/Th1), as well as the plasticity of Th17 cells, i.e. their property to shift to Th1 in presence of IL-12. The plasticity of Th17 to Th1 cells was recently confirmed in mice, where it was even found that Th17 cells behave as pathogenic only when they shift to Th1 cells. Studies in humans have also shown that memory Th17 are different than in mice because virtually all of them express CD161. A positive correlation between presence of CD4+ CD161+ T cells in the synovial fluid of children with juvenile idiopathic arthritis and indicators of disease activity was found. They were Th17/Th1 and Th1 cells originated from local shifting of Th17 cells to IFN-gamma poduction. While murine Th17 cells are thought to derive from naive CD4+ T cells in response to IL-6 and TGF-beta, human Th17 cells originate from thymic CD4+ CD161+ T-cell precursors in response to IL-1b and IL-23. TGF-beta indirectly favours development of human Th17 cells through the inhibition of both T-bet expression and development of Th1 cells. Very recently, Th17 cells have been detected in the thymus of wild-type mice and TGF-beta was found to be dispensable also for murine Th17 differentiation. Thus, studies in humans have depicted Th17 cells better than studies in mice.