These studies will use techniques of in vitro monitoring combined with modulation of immune reactivity by quality-controlled rabbit anti-thymocyte globulin (RATG) to: 1) Study the potential of these systems to reduce incompatible allograft rejection rates. 2) Study the potential of the systems to improve patient survival by effecting a more appropriate and selective immunosuppression to reduce infectious complications. 3) To assess the capability of in vitro immunological monitoring parameters to accurately diagnose a pre-rejection state or early graft rejection. 4) To utilize in vitro systems of immune monitoring and their in vivo rejection correlates to probe the mechanisms of human allograft rejection. This study will use a randomized double-blind technique to evaluate the efficacy of individualized monitoring and modulation of immune reactivity using two different quality-controlled RATG preparations. In vitro studies will focus on parameters of: 1) T cell numbers and reactivity, 2) T cell cytotoxicity, 3) suppressor cell activity, 4) B cell numbers and reactivity, and 5) antibody-dependent cell-mediated cytotoxicity (ADCC). Three of these parameters - 1) T cells levels, 2) T cell reactivity and 3) ADCC specific to donor - have shown promise of providing a rational basis for individualized modulation of recipient immune reactivity using RATG. The other in vitro parameters will be used to study the putative role of these factors in rejection or facilitation of cadaver kidney allografts in ATG-treated recipients. The in vitro measurements provide possible means of acheiving more optimal immunosuppression by potent, appropriate and selective depression of reactivity germane to allograft rejection, and relative preservation of immune reactivity against infection. These techniques also offer potential for better insights into immune mechansisms in 1) allograft rejection and 2) facilitation of allograft survival.
NIH ExPorter
NIH ExPorter