IMMUNOLOGICAL RESPONSES TO INJURY AND GRAFTING IN THE CENTRAL-NERVOUS-SYSTEM OF NONHUMAN-PRIMATES

Allogeneic transplantation for the therapy of human Parkinson's diseas e is being considered as a viable approach at several clinical centers worldwide, As an attempt to understand the basic biology of central n ervous system (CNS) transplantation, our laboratory has del eloped an experimental nonhuman primate model for human Parkinson's disease and carried out preliminary studies directed at evaluating the potential p athology at the graft site, In addition, studies have been conducted t o examine whether such transplantation procedures lead to specific and /or nonspecific immunologic sensitization of the host or results in ge neralized immunosuppression. Groups of rhesus macaques (Macaca mulatta ) were either controls operated (n = 6), autografted with adrenal medu llary and peripheral nerve tissue (n = 3), or allografted with fetal m esencephalic tissue (n = 6), Immunohistological studies demonstrated t he presence of mononuclear cell infiltrates as early as 1 wk and up to 1 yr postoperatively, although the frequency of the infiltrating cell s declined with time, The infiltrates consisted of variable numbers of cells which express CD2+, CD3+, CD4+, CD8+, CD19+, CD22+, CD25+, and CD68+, There appeared to be no difference in the frequency, kinetics, or phenotype of the infiltrating cells in operative controls compared with recipients of auto-or allografts, Tissue sections obtained postop eratively showed low levels of major histocompatibility complex (MHC) Class I antigens and no detectable level of MHC-Class II antigens in n eural tissue, A small aliquot of tissue from the operative site was pl aced in vitro with media containing interleukin-2 (IL-2), which led to the exudation and growth of mononuclear cells that were predominantly CD4+ cells, Phenotypic studies of peripheral blood mononuclear cells (PBMC) from operative controls, auto-and allograft recipient monkeys p erformed at varying time periods postoperatively failed to show differ ences in the frequencies of subsets of T-cells, B-cells, NK-cells, or monocytes, Studies on aliquots of the same PBMC failed to show major f unctional differences in NK-cells, LAK cells, or response to polyclona l mitogens, Finally, recipients of allogeneic mesencephalic grafts fai led to show evidence of donor-specific humoral or cellular sensitizati on, These data indicate that transplantation of autograft adrenal or a llograft fetal mesencephalic tissues in the CNS of nonhuman primate di d not induce detectable donor-specific sensitization nor nonspecific i mmunosuppression, (C) 1998 Elsevier Science Inc.