Fas-mediated cytotoxicity by gamma delta T cells during acute rejection inxenotransplantation of spheroidal aggregate-cultured hepatocytes

Xenogeneic transplantation has recently become a subject of interest for th e transplantation community due to the current organ shortage, which could be partially or even totally solved by the development of this strategy. Ho wever, xenogenetic rejection remains a formidable barrier preventing such u se in a clinical setting. The spheroidal aggregate-cultured hepatocytes of WKA rats were injected into the spleen of C3H mice, and quantitative assess ment of transplanted xenogeneic hepatocytes using Tc-99m-GSA demonstrated t hat hepatocytes decreased dramatically 2 days after transplantation (day 2) and few viable hepatocytes in spheroids were detected on day 3. The NK act ivity significantly increased on day 1, and gamma delta receptor/FasL-expre ssing T cells appeared on day 2. These results suggested that xenogeneic cy totoxicity consisted of gamma delta T cells through the Fas/Fas ligand syst em, as well as non-T-cell-mediated cellular response, in the MHC-unrestrict ed pathway in this intrasplenically transplanted xenogeneic hepatocyte mode l.