Successful organ transplantation is a lifesaving procedure, but it is met with serious risks including organ rejection, infection, and a compromised immune system. This study aims to identify new therapeutic strategies to yield transplant acceptance while reducing the reliance on immunosuppression. A previously developed ordinary differential equation model of the immune response to a transplant is adapted to incorporate the effect of immunosuppression in combination with the adoptive transfer of regulatory T cells. Known mechanisms through which calcineurin inhibitors (immunosuppressive drugs) preserve the transplant are simulated. The model is used to show that the combined use of adoptive transfer provides little additional benefit, even when tapering immunosuppression levels. Model simulations also demonstrate the impact of reducing the effect of immunosuppression on regulatory T cells, with the aim of reducing key mechanisms of immunosuppression but still achieving graft tolerance. The study demonstrates the utility of mathematical modeling in guiding future experimental studies of new therapeutic strategies in transplant immunology.
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