TEMPORAL PATTERN OF HOST RESPONSES AGAINST INTRASTRIATAL GRAFTS OF SYNGENEIC, ALLOGENEIC OR XENOGENEIC EMBRYONIC NEURONAL TISSUE IN RATS

The host response to immunologically incompatible intrastriatal neural grafts was studied using immunohistochemical techniques. Dissociated ventral mesencephalic tissue from embryonic donors of either syngeneic , allogeneic or xenogeneic (mouse) origin was stereotaxically implante d into adult rats. The brains were analysed 4 days, 2 weeks or 6 weeks after grafting with antibodies against the following antigenic struct ures: major histocompatibility complex (MHC) class I antigens; MHC cla ss II antigens; complement receptor (CR) 3 (marker for microglia and m acrophages); helper T-lymphocyte antigen-cluster of differentiation (C D) 4; cytotoxic T-lymphocyte antigen-CD8; tyrosine hydroxylase (TH) (m arker for transplanted dopaminergic neurons). The number of surviving TH-positive cells was not different at the various time points in eith er the syngeneic or allogeneic groups, whereas the xenogeneic cells we re all rejected by 6 weeks. The host reactions were similar in charact er in the syngeneic and allogeneic groups. At 4 days after implantatio n, there were increased levels of expression of MHC class I and II ant igens. In and around the grafts, there were cellular infiltrates consi sting of activated microglia, macrophages, CD4- and CD8-positive lymph ocytes. At 6 weeks, MHC expression was reduced and the cellular infilt rates had subsided with only low numbers of activated microglia cells and CD8-positive lymphocytes remaining. In the xenogeneic group, at 4 days, some grafts contained cavities, possibly reflecting acute reject ion. At later stages, the xenografts were heavily infiltrated by macro phages, activated microglial cells and T-lymphocytes, and at 6 weeks a ll the xenografts were rejected. Taken together, the results suggest t hat there is an inflammation caused by the implantation process which leads to an accumulation of host defence cells. This, in turn, leads t o increased MHC expression in and around the grafts. In syngeneic graf ts, these reactions are short lasting and weak; for allografts slightl y more pronounced and longer lasting than syngeneic grafts, but not su fficient to cause rejection. For xenografts, the reactions are more in tense and lead to transplant rejection. Thus, a strong sustained infla mmatory response may be an important determinator for the failure of h istoincompatible neural grafts. It can be speculated that a short-term anti-inflammatory treatment of graft recipients may be a sufficient i mmuno-suppressive regimen to allow long-term graft survival.