Interleukin-17-producing gammadelta+ T cells protect NOD mice from type 1 diabetes through a mechanism involving transforming growth factor-beta.

Whether interleukin (IL)-17 promotes a diabetogenic response remains unclear. Here we examined the effects of neutralization of IL-17 on the progress of adoptively transferred diabetes. IL-17-producing cells in non-obese diabetic (NOD) mice were identified and their role in the pathogenesis of diabetes examined using transfer and co-transfer assays. Unexpectedly, we found that in vivo neutralization of IL-17 did not protect NOD-severe combined immunodeficiency (SCID) mice against diabetes transferred by diabetic splenocytes. In NOD mice, gammadelta(+) T cells were dominated by IL-17-producing cells and were found to be the major source of IL-17. Interestingly, these IL-17-producing gammadelta T cells did not exacerbate diabetes in an adoptive transfer model, but had a regulatory effect, protecting NOD mice from diabetes by up-regulating transforming growth factor (TGF)-beta production. Our data suggest that the presence of IL-17 did not increase the chance of the development of diabetes; gammadelta T cells protected NOD mice from diabetes in a TGF-beta-dependent manner, irrespective of their role as major IL-17 producers.