Immunosuppressive effect of arsenic trioxide on islet xenotransplantation prolongs xenograft survival in mice

The role of arsenic trioxide (As(2)O(3)) in inhibiting immune rejection and prolonging islet allograft survival has been identified in islet allotransplantation. This study aims to explore the role of As(2)O(3) in islet xenotransplantation and the action mechanism. The streptozotocin (STZ) was used in C57BL/6 mice to induce the type 1 diabetes mellitus (T1DM) for xenotransplantation models establishment. Donor islets were isolated by digesting. The flow cytometry (FCM) was used to analyze lymphocyte types. The blood sugar level was detected by using intraperitoneal glucose tolerance test (IPGTT). The serum level of cytokines was determined by the enzyme-linked immunosorbent assay (ELIZA). The cell proliferation was measured by MTT assay. The mRNA levels were quantified with qRT-PCR. As(2)O(3) prolonged the survival of the recipient mice but had no influence on body weight. As(2)O(3) protected the function of xenograft in insulin secretion and suppressed immune rejection of recipient. As(2)O(3) inhibited proliferation of T lymphocyte and increased the proportion of Foxp3(+) regulatory T cells in recipient mice. As(2)O(3) inhibited activation and promoted clonal anergy of T lymphocyte. As(2)O(3) decreased total number of B cells and reduced partial antibody levels in recipient mice. As(2)O(3) and leflunomide showed a synergistic effect in suppressing islet xenotransplant rejection. As(2)O(3) prolongs islet xenograft survival by inhibiting cellular immune response, and increasing Foxp3(+) regulatory T cells, while decreasing partial antibody levels in serum.