Migration of xenogenic astrocytes in myelinated tracts: a novel probe for immune responses in white matter

Summary Experimental brain transplantation allows the study of the development of the immune response against brain antigens within the brain itself. This laboratory has developed a transplantation model in which rabbit embryo brain fragments are placed in the brains of newborn mice. The migration of xenogenic astrocytes is traced by a monoclonal antibody which combines with donor but not host glial fibrillary acidic protein. In the first 4 weeks after transplantation, the donor astrocytes successfully migrate, often within myelinated tracts. Following this period, T cells make their apperance and xenogenic astrocytes disappear by 10 weeks. The propensity for clearly identified foreign astrocytes to migrate in myelinated tracts coupled with a well-defined time course of host-vs-graft interaction suggested that the model could be used to study the immune response in white matter. The studies reported here provide sequential examples of the relationship between migration by foreign astrocytes in myelinated tracts and the development of the host immune response. Extensive migration in white matter tracts was first observed in the absence of any T cell response. Subsequently T cells were found at the transplantation site. Finally Ia was found to be expressed on blood vessels and microglia were strongly reactive in white matter that contained T cells but no foreign astrocytes. These observations support the suggestion that the model can be used to more precisely define cellular immune events that occur within white matter.Supported by the Veterans Administration (US), the Ministère de la Recherche et de la Technologie, and the Philippe Foundation (Paris and New York) (sabbatical support provided to J. Booss) INSERM, the Association pour la Recherche sur la Sclérose en Plaques (ARSEP) and the Myelin Project Foundation