The immunosuppression effects of deforolimus (ridaforolimus, AP23573) on allograft organ transplantation

Abstract

Abstract Objects We conducted this study to confirm the immunosuppression effect of Deforolimus in heart allotransplantation and find its mechanism. Material and methods We used vitro methods to confirm the immunosuppression of Deforolimus in T cell subgroups. Then, we conducted heart allotransplantation from BALB/c donors to C57BL/6 recipients with the oral administration of Deforolimus or blank solvent to contrast the immunosuppression effect in vivo. We used the flow cytometry（）, clone anergy test, ELISA (enzyme‐linked immunosorbent assay), apoptosis test, and lymphocyte translation (LT) to find the mechanism of Deforolimus’ immunosuppressive action. Results Studies in vitro demonstrated that Deforolimus had immunosuppressive action. Studies in vivo demonstrated that Deforolimus could inhibit the immune system of the heart allotransplantation recipients to extend the recipients’ life. The mechanisms of Deforolimus’ immunosuppressive action included induction of Tregs (regulatory T cells), induction of T cells anergy, and decreasing proportion of T cells in spleens and lymph nodes. Conclusion Deforolimus suppressed the immunological rejection of mouse cardiac allotransplantation which laid the foundation of Deforolimus applying to solid organ allotransplantation.

Keywords

• deforolimus
• heart allotransplantation
• immunosuppression