Microbial lipopeptides induce the production of IL-17 in Th cells

Naive Th cells can be directed in vitro to develop into Th1 or Th2 cells by IL-12 or IL-4, respectively. In vivo, chronic immune reactions lead to pol arized Th cytokine patterns. We found earlier that Borrelia burgdorferi, th e spirochaete that causes Lyme disease, induces Th1 development in cup TCR- transgenic Th cells. Here, we used TCR-transgenic Th cells and oligonucleot ide arrays to analyze the differences between Th1 cells induced by IL-12 vs those induced by B, burgdorferi. Transgenic Th cells primed with peptide i n the presence of B, burgdorferi expressed several mRNAs, including the mRN A encoding IL-17, at significantly higher levels than Th cells primed with peptide and;IL-12 Cytometric single-cell analysis of Th cell cytokine produ ction revealed that IL-17 cannot be categorized as either Th1 or Th2 cytoki ne, Instead, almost all IL-17-producing Th cells simultaneously produced TN F-alpha and most IL-17(+) Th cells also produced GM-CSF. This pattern was a lso observed in humans. Th cells from synovial fluid of patients with Lyme arthritis coexpressed IL-17 and TNF-alpha upon polyclonal stimulation. The induction of IL-17 production in Th cells is not restricted to B. burgdorfe ri, Priming of TCR-transgenic Th cells in the presence of mycobacterial lys ates also induced IL-17/TNF-alpha coproduction, The physiological stimulus for IL-17 production was hitherto unknown, We show here for the first time that microbial stimuli induce the expression of IL-17 together with TNF-alp ha in both murine and human T cells. Chronic IL-17 expression induced by mi crobes could be an important mediator of infection-induced immunopathology.