Comparative Inhibitory Effects of Tacrolimus, Cyclosporine, and Rapamycin on Human Anti‐Pig Xenogeneic Mixed Lymphocyte Reactions

• DOI: 10.1111/xen.12876
• Publication Date: 2024-07-19T10:19:35Z
• Authors: Man Zhang; Hao Feng; Jiaxiang Du; Song Chen; Lan Zhu; Yi Wang; Dengke Pan; Gang Chen
• Keywords: Xenotransplantation; Mixed lymphocyte reaction; CD154

ABSTRACT Background Long‐term immunosuppressive maintenance therapy is necessary to prevent the rejection of xenografts. However, it still unclear which oral immunosuppressant most suitable for pig‐to‐human xenotransplantation . Methods A xenogeneic mixed lymphocyte reaction (MLR) system was established using peripheral blood mononuclear cells (PBMCs) isolated from wildtype (WT) or GTKO/CMAHKO/β4GalNT2KO (TKO) pigs as stimulator and human PBMCs responder cells. Various concentrations tacrolimus (Tac), cyclosporine (CsA), rapamycin (Rapa) were added MLR interventions. The inhibitory effects three immunosuppressants on proliferation cytokine production T studied compared. effect anti‐CD154 mAb alone in combination with Tac/CsA/Rapa xenoreactive also investigated. Results both WT TKO stimulated significant Tac had a strong T‐cell by pig PBMCs. CsA inhibited typical dose‐dependent manner. When reached 5 200 ng/mL, respectively, rates CD3 + /CD4 /CD8 reduced almost negative level. Even at high concentrations, Rapa only moderate MLR. these responses further confirmed detection CD25 expression supernatant cytokines (IL‐2, IL‐6, IFN‐γ, TNF‐α, IL‐4, IL‐10, IL‐17). Although monotherapy showed proliferation, low‐dose combined Tac, CSA, could produce synergistic effects. Conclusion more efficient than inhibiting vitro. If used mAb, all can achieve satisfactory