Regulatory Effect of γδ T Cells on IL-17+ Uveitogenic T Cells

PURPOSE. To characterize the regulatory effect of gamma delta T cells in the activation of IL-17(+) uveitogenic T cells. METHODS. The authors administered the gamma delta TCR-specific antibody GL3 to B6 mice before or after antigen immunization and examined Th1- or Th17-polarized T-cell responses. The intensity of Th17 responses was also examined in responder T cells containing varying numbers of gamma delta T cells. RESULTS. GL3 treatment resulted in varying degrees of depletion of circulating gamma delta T cells, depending on when the antibody was administered. The intensity of the alpha beta TCR+IL-17(+), but not the alpha beta TCR+IFN-gamma(+), IRBP-specific T-cell responses was correlated to the percentage of gamma delta T cells in the responder T cells. Kinetic studies showed that early IL-17(+) T cells were primarily gamma delta T cells, with a later gradual shift to alpha beta T cells. A close association was seen between the intensity of the IL-17(+) autoreactive T-cell response and the percentage of gamma delta T cells in the responder T cells. Although a modest increase in gamma delta T cells among the responder T cells promoted the expansion of IL-17(+) alpha beta TCR+ T cells, a higher proportion of gamma delta T cells inhibited it. CONCLUSIONS. gamma delta T cells are actively involved in the generation of alpha beta TCR+IL-17(+) T cells. The number of gamma delta T cells and the alpha beta/gamma delta T-cell ratio in the responder T cells regulate the intensity of the Th17-type autoreactive T-cell response. (Invest Ophthalmol Vis Sci. 2010; 51: 4661-4667) DOI: 10.1167/iovs.09-5045