Vγ4 γδ T Cells Provide an Early Source of IL-17A and Accelerate Skin Graft Rejection.

Activated γδ T cells have been shown to accelerate allograft rejection. However, the precise role of skin-resident γδT cells and their subsets - Vγ5 (epidermis), Vγ1 and Vγ4 (dermis) - in skin graft rejection have not been identified. Here, using a male to female skin transplantation model, we demonstrated that Vγ4 T cells, rather than Vγ1 or Vγ5 T cells, accelerated skin graft rejection and that IL-17A was essential for Vγ4 T cell-mediated skin graft rejection. Moreover, we found that Vγ4 T cells were required for early IL-17A production in the transplanted area, both in skin grafts and in the host epidermis around grafts. Additionally, the chemokine (C-C motif) ligand 20 (CCL20)-chemokine receptor 6 (CCR6) pathway was essential for recruitment of Vγ4 T cells to the transplantation area, whereas both IL-1β and IL-23 induced IL-17A production from infiltrating cells. Lastly, Vγ4 T cell-derived IL-17A promoted the accumulation of mature dendritic cells in draining lymph nodes to subsequently regulate αβ T cell function after skin graft transplantation. Taken together, our data reveal that Vγ4 T cells accelerate skin graft rejection by providing an early source of IL-17A.