The overall objective is to perform composite tissue allotransplantation without the use of long-term systemic immunosuppression. The induction of donor-specific tolerance would permit significant advances in reconstructive surgery and burn treatment, where autologous sources of tissue are inadequate or absent. Dendritic cells (DCs) are highly specialized antigen presenting cells (APCs) that induce and regulate immune responses. Bone marrow-derived DCs pulsed with donor splenocyte lysate and combined with a regimen including anti-lymphocyte serum (ALS) and a short course of cyclosporine has been shown to result in long- term acceptance of all tissue types of a composite tissue allograft (CTA) except skin. We hypothesize that pulsing """"""""tolerogenic"""""""" DCs with donor skin antigen in addition to donor major histocompatibility complex (MHC) alloantigens will promote long-term survival of skin as well as the other components of a CTA in a full MHC barrier rat model. The influence of skin antigen-pulsed DCs on local and systemic immune responses following CTA transplantation will be evaluated by histology, immunohistochemistry, cytokine profiles, serum antibody detection, CML, MLR, adoptive cell transfer studies, and RT PCR Foxp3 expression. ? ? ?
| Solari, Mario G; Thomson, Angus W (2008) Human dendritic cells and transplant outcome. Transplantation 85:1513-22 |
