In Vitro Evaluation of Basiliximab as an Induction Therapy for Xenotransplantation.

Abstract

Background: Induction therapy is necessary to prevent acute rejection of xenografts. At present, basiliximab is rarely used as an induction therapy agent in solid organ xenotransplantation. In this study, we conducted in vitro experiments to investigate the inhibitory effect of basiliximab on human anti-porcine xenogeneic immune responses.

Methods: A xenogeneic and allogeneic mixed lymphocyte reaction (MLR) system was established using peripheral blood mononuclear cells (PBMCs) isolated from GTKO/CMAHKO/β4GalNT2KO (triple-knockout, TKO) pigs or humans as stimulator cells, and another group of human PBMCs as responder cells. Various concentrations of basiliximab were added to the MLR systems as interventions. The inhibitory effects of basiliximab on the proliferation and cytokine production of human T cells were compared.

Results: PBMCs from TKO pigs or humans stimulated significant proliferation of human T cells. Basiliximab inhibited human CD4⁺ and CD8⁺ T-cell proliferation in a typical dose-dependent manner in both xenogeneic and allogeneic MLR. When the concentration of basiliximab reached 1 µg/mL, the proliferation rates of xenoreactive CD4⁺ and CD8⁺ T cells decreased by more than 72%, which was quite similar to the effect in the allogeneic MLR. The inhibitory effects of basiliximab on xenogeneic T-cell responses were further confirmed by the detection of CD25 expression and supernatant cytokines (IFN-γ, TNF-α), and the results were similar to those for allogeneic MLR.

Conclusions: Basiliximab can significantly reduce the xenoreactivity of human lymphocytes against TKO pig cells, and its inhibitory effect is no less than that on allogeneic T cell responses, supporting its potential as induction therapy in xenotransplantation.