Background.The precise mechanisms involved in islet xenograft rejection remain unknown. The purpose of the present study was to determine cellular mechanisms responsible for islet xenograft rejection in the liver to facilitate finding a procedure for prevention of immune rejection.Methods.Hepatic mononuclear cells (MNC) as well as splenocytes, peripheral blood MNC, and thymocytes from streptozotocin-induced diabetic mice (BALB/c) rejecting the intrahepatic rat (Lewis) islet xenografts were isolated and examined by two-color FACS analysis.Results.The characteristic finding of the hepatic MNC from the mice rejecting islet xenografts compared with mice receiving isografts was a significant increase in the yield as well as in the percentage of the cells expressing CD3+interleukin-2 receptor (IL-2R) α-β+, CD3+CD8α+β+, and T cell receptor (TCR) αβ+lymphocyte function-associated antigen-1+. The expression of CD3 and TCRαβ of these T cells was found to be of intermediate intensity (TCRintcells). The expansion of these TCRintcells occurred predominantly in the liver. There was no significant difference in the cells expressing CD3+IL-2Rα+, CD3+CD4+, CD3+TCRγδ+, CD3-IL-2Rβ+(natural killer cells), and B220+(B cells). In vivo administration of anti-IL-2Rβ monoclonal antibody directed to the expanded cells produced a prevention of rejection.Conclusions.These findings suggest that islet xenograft rejection in the liver from rat to mouse is an event for which the TCRintcells are responsible.