Background: Identifying effective immunosuppressive strategies is critical for addressing immunological rejection following organ transplantation. This study explores the potential immunosuppressive effects and mechanisms of temsirolimus, a rapamycin derivative, in organ transplantation.
Methods: A mouse cardiac allograft model was established using a cervical cannula technique with BALB/c donors and C57BL/6 recipients. Mice were administered temsirolimus intragastrically and graft survival was evaluated. Histological staining was used to assess pathological changes. The BrdU assay was used to measure splenic T cell proliferation. Flow cytometry was used to quantify regulatory T cells (Tregs), CD4+ T cells, and CD8+ T cells. ELISA and qPCR assays were used to determine Foxp3, IL-4, IFN-γ, and TGF-β expression.
Results: Temsirolimus displayed potent immunosuppressive effects at 20 mg/kg/day, significantly inhibiting T cell proliferation (84.6%, P < 0.0001) and prolonging graft survival (median 49 days vs. 8.5 days in controls, P < 0.0001). However, median survival decreased to 34.5 days upon withdrawal. Temsirolimus also reduced splenic CD4+ and CD8+ T cells (2.85% and 2.92%, P < 0.001) and antibody levels (IgM, IgG1, IgG2) by 11.85-29.09% (P < 0.0001) and increased Tregs, Foxp3, IL-4 (P < 0.01), and TGF-β (P < 0.05), while decreasing IFN-γ (P < 0.001).
Conclusions: Temsirolimus exhibited potent immunosuppressive effects, emerging as a strong candidate to mitigate organ transplant rejection.
Keywords: Allograft survival; Immunosuppressive effect; Organ transplantation; Temsirolimus; Tregs.
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