V Gamma 4 Gamma Delta T Cells Provide An Early Source Of Il-17a And Accelerate Skin Graft Rejection

Activated gamma delta T cells have been shown to accelerate allograft rejection. However, the precise role of skin-resident gamma delta T cells and their subsets-V gamma 5 (epidermis), V gamma 1, and V gamma 4 (dermis)-in skin graft rejection have not been identified. Here, using a male to female skin transplantation model, we demonstrated that V gamma 4 T cells, rather than V gamma 1 or V gamma 5 T cells, accelerated skin graft rejection and that IL-17A was essential for V gamma 4 T-cell-mediated skin graft rejection. Moreover, we found that V gamma 4 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-chemokine receptor 6 pathway was essential for recruitment of V gamma 4 T cells to the transplantation area, whereas both IL-1 beta and IL-23 induced IL-17A production from infiltrating cells. Lastly, V gamma 4 T-cell-derived IL-17A promoted the accumulation of mature dendritic cells in draining lymph nodes to subsequently regulate alpha beta T-cell function after skin graft transplantation. Taken together, our data reveal that V gamma 4 T cells accelerate skin graft rejection by providing an early source of IL-17A.