Although much research has been done on the characterization and function of transplanted neural tissue, most studies have focused on the neuronal and macroglial elements of the transplant, ignoring a significant group of cells within the central nervous system (CNS), i.e. the microglial cells. The proposed research is designed to address several fundamental questions as to the functional role of microglia within transplanted neural tissue. The hypothesis that microglia, the resident immunocompetent tells of the CNS, are the cellular component most likely responsible for the initiation of immunological rejection of allo- and xenografted neural tissue will be tested. Fetal spinal cord tissue will be depleted of microglia and allografted (using two histo-incompatible rat strains) and xenografted (using two incompatible species) into injured host spinal cords, and the immunogenicity of the transplant assessed, i.e. presence and severity of the host immune response. To complement the depletion experiment, purified suspensions of microglial cells will be allografted into a histoincompatible rat spinal cord in order to test the hypothesis that microglia are capable of initiating a host-derived immune response against the graft. This project differs from previous studies, however, in that the microglia will be indelibly labelled with a genetic marker prior to transplantation, allowing the cells to be identified and traced in the host spinal cord. Furthermore, label led microglia will be transplanted into immunologically tolerant animals, i.e. in which they will not be rejected, in order to test the hypothesis that transplanted microglia have beneficial effects, such as neurotrophic properties and ability to lay down extracellular matrix components. The proposed study should provide a comprehensive examination of the possible beneficial and detrimental roles of microglial cells in neural transplantation, a subject about which very little is known.
