Molecular and cellular mechanisms in immune rejection of intracerebral neural transplants

Restorative transplantation of human embryonic nigral tissue for Parkinson's disease has given encouraging results with functional benefit and minimal signs of rejection in patients receiving standard immunosuppression. Due to the limited availability of human donor material and ethical concerns with its use, porcine tissue is considered an appropriate alternative. In animal studies, neural allo- and xenografts are usually rejected in the brain, emphasizing the necessity of understanding factors underlying survival and rejection of intracerebral neural transplants. Here, we review fundamental mechanisms of allo- and xenograft rejection, and discuss the privileged immune status of the brain, and how we may take advantage of this in order to improve and secure graft survival. Rejection of neural xenografts is expected to be of a cellular nature, like neural allograft rejection, but may also display unique features, and cannot be dealt with using conventional immunosuppressive therapies. The challenge therefore is to improve existing and design new strategies that allow permanent survival of histoincompatible neural grafts, taking advantage of the special immune status of adult CNS and immature donor brain tissue.