Modeling rejection immunity

Background Transplantation is often the only way to treat a number ofdiseases leading to organ failure. To overcome rejection towards the trans-planted organ (graft), immunosuppression therapies are used, which haveconsiderable side-effects and expose patients to opportunistic infections. Thedevelopment of a model to complement the physician's experience in speci-fying therapeutic regimens is therefore desirable.The present work proposes an Ordinary Differential Equations model ac-counting for immune cell proliferation in response to the sudden entry ofgraft antigens, through different activation mechanisms. The model consid-ers the effect of a single immunosuppressive medication (e.g. cyclosporine),subject to first-order linear kinetics and acting by modifying, in a saturableconcentration-dependent fashion, the proliferation coefficient. The latter hasbeen determined experimentally. All other model parameter values havebeen set so as to reproduce reported state variable time-courses, and tomaintain consistency with one another and with the experimentally derivedproliferation coefficient.Results The proposed model substantially simplifies the chain of eventspotentially leading to organ rejection. It is however able to simulate quanti-tatively the time course of graft-related antigen and competent immunore-active cell populations, showing the long-term alternative outcomes of rejec-tion, tolerance or tolerance at a reduced functional tissue mass. In particu-lar, the model shows that it may be difficult to attain tolerance at full tissuemass with acceptably low doses of a single immunosuppressant, in accordwith clinical experience.Conclusions The introduced model is mathematically consistent with knownphysiology and can reproduce variations in immune status and allograft sur-vival after transplantation. The model can be adapted to represent differenttherapeutic schemes and may offer useful indications for the optimization oftherapy protocols in the transplanted patient