CD8+ gamma delta regulatory T cells induced by oral exposure to alloantigen play a role in prolongation of kidney transplant survival in rats

Our lab has previously shown that oral administration of alloantigen prior to transplantation significantly prolongs kidney allograft survival. This prolongation is mediated by intragraft CD8+ T regulatory (Treg) cells in an antigen specific manner. We hypothesize that the cell responsible is a CD8+gammadelta Treg cell. Adoptive transfer of gammadelta GICs significantly prolonged allograft survival. A two fold increase in CD8+gammadelta T cells was detected in the allografts of alloantigen pre-fed animals. These cells expressed the Foxp3 transcription factor and produced increased levels of IL-4 and IL-10. Flow cytometric analysis detected increased numbers of CD8+gammadelta T cells in the spleen of alloantigen pre-fed animals and a decrease in CD8 +gammadelta T cells in the MLN upon transplantation. Our results support a model in which oral tolerance to alloantigen induces CD8 +gammadelta Treg cells in the MLN that migrate to the allograft upon transplantation where they secrete Th2 cytokines to suppress Th1 rejection response.