| gammadelta T cells contribute uniquely to host immune competence, but how they do so remain unclear. By analyzing T10/T22-specific gammadelta T cells in mice with different T10/T22 expression patterns, we find that encountering antigen in the thymus is neither required nor inhibitory for the development of these cells. In the absence of ligand recognition, we suggest a plausible mechanism whereby gammadelta TCR self-dimerization may be sufficient to drive gammadelta thymocyte development. Instead, ligand recognition determines, in large part, which of two distinct functional subsets gammadelta T cells will become. When triggered through the TCR, lymphoid-gammadelta T cells of the spleen and thymus that encounter ligand during development produce IFNgamma, while those that develop in the absence of ligand make IL-17, a major inducer of granulopoiesis during inflammation. Indeed, we find large fractions of IL-17+ gammadelta T cells from draining lymph nodes immediately after peptide/CFA immunization and days before the appearance of antigen specific IL-17+ alphabeta T cells. This suggests a critical role for gammadelta T cells as 'initial providers' of IL-17 in an inflammatory response to novel antigens. |
