Transplantation immunology and the central nervous system

Controlled clinical trials of cell transplantation for Parkinson's disease yielded disappointing results. Significant long-term functional improvement was not observed and cell survival was low. Although the brain was traditionally considered as "immunologically privileged" recent findings demonstrated late increase in the number of microglia around the grafts, therefore implying an involvement of immune mechanisms. The immunology of organ and cell transplantation to other body locations is scrupulously investigated and significant stepping-stones have been achieved. Ample evidence regarding the role of antigen-presenting cells in graft rejection has been documented. However, this knowledge did not benefit the discipline of cell transplantation to the central nervous system, and the minimal consideration of potential immune responses remain empirical in nature. In this review we summarize current knowledge of the major histo-compatibility complex and its role in transplant immunology. Resident cells of the brain that take part in immune responses are also discussed. Based on this information we hypothesize that the immune mechanisms involved with the long-term graft failure of cell transplantation to the central nervous system are likely to be chronic, and not acute, rejection. This, in turn, should have significant importance in the choice of anti-rejection drugs to be used.