REJECTION OF WILD-TYPE AND GENETICALLY-ENGINEERED MAJOR HISTOCOMPATIBILITY COMPLEX-DEFICIENT GLIAL-CELL XENOGRAFTS IN THE CENTRAL-NERVOUS-SYSTEM RESULTS IN BYSTANDER DEMYELINATION AND WALLERIAN DEGENERATION

Mixed glial cell cultures prepared from neonatal wild type and mutant male mice lacking either major histocompatibility complex class I, cla ss II or both class I and II molecules (major histocompatibility compl ex class (III0/0)-I-0/0), and from syngeneic male rats were transplant ed into female rat spinal cord white matter. Graft survival was monito red using DNA probes specific to the Y chromosome. Survival of major h istocompatibility complex class-deficient grafts was not prolonged com pared to wild-type grafts and in most cases grafts could not be detect ed at 28 days post-transplantation, at which lime syngeneic grafts wer e still present. However, rejection of xenografts resulted in signific ant bystander damage to host tissue. In recipients of wild-type and ma jor histocompatibility complex class I-0/0 xenografts the predominant pathology was demyelination. Demyelination was also observed in recipi ents of major histocompatibility complex class II0/0 and major histoco mpatibility complex class (III0/0)-I-0/0 xenografts, however in additi on there was marked collagen deposition and meningeal cell invasion. S ignificantly more axons had undergone Wallerian degeneration in recipi ents of major histocompatibility complex class II0/0 and major histoco mpatibility complex class (III0/0)-I-0/0 xenografts than recipients of wild-type and major histocompatibility complex class I-0/0 xenografts . These findings were interpreted as evidence of a more destructive im mune response associated with rejection of grafts lacking major histoc ompatibility complex class II molecules. It was proposed that the diff erence in the severity of bystander damage may be related to the previ ously demonstrated ability of xenogeneic major histocompatibility comp lex class II molecules to activate host T cells directly, whereas xeno grafts lacking major histocompatibility complex class II molecules wer e capable of activating host T cells only by the indirect pathway. (C) 1998 IBRO. Published by Elsevier Science Ltd.