title: Haplotype matching is not an essential requirement to achieve remyelination of demyelinating CNS lesions.
abstract: Transplantation of oligodendrocyte precursor cells (OPCs) results in efficient remyelination in animal models of demyelination. However, the experiments so far undertaken have not addressed the need for tissue-type matching to achieve graft-mediated remyelination. Examination of MHC expression (main determinant of allograft rejection) by OPCs showed nondetectable levels under standard culture conditions and upregulation of MHC Class I expression only upon exposure to interferon gamma. We therefore hypothesized that MHC matching of OPC grafts may not be crucial to achieve transplant-mediated remyelination. Transplant experiments performed using a nonself repairing toxin-induced demyelination model showed that, similarly to allogeneic neurons, survival of allogeneic oligodendrocyte lineage cells is influenced by donor-host haplotype combination and graft composition. Transplantation of allogeneic mixed glial cell cultures resulted in remyelination failure by 1 month postengraftment due to a rejection response targeting both myelinating oligodendrocytes and OPCs, suggesting that inflammation-induced upregulation of OPC MHC I expression results in susceptibility to cytotoxic T cell attack. In contrast, remyelination persisted for at least 2 months following transplantation of OPC-enriched cultures whose overall MHC expression level was significantly decreased. While OPC-enriched preparations elicited delayed type hypersensitivity responses in hosts sensitized to alloantigens, allografting of such preparations into a central nervous system demyelinating lesion did not result in recipient priming. We conclude that while allografted oligodendrocyte lineage cells become targets of a graft rejection response once this response has been initiated, transplantation of OPC-enriched preparations can evade priming against alloantigens and graft rejection. This finding indicates that close tissue matching may not be an essential requirement for successful transplant-mediated remyelination.
authors.affiliation: Department of Veterinary Medicine, MS Society Cambridge Centre for Myelin Repair, Cambridge Centre for Brain Repair, Cambridge, United Kingdom. vanja.tepavcevic@chups.jussieu.fr
authors.forename: V
authors.initials: V
authors.lastname: Tepavcević
authors.forename: W F
authors.initials: WF
authors.lastname: Blakemore
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D003711:Demyelinating Diseases / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology*; D006239:Haplotypes / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods / Q000592:standards; D007111:Immunity, Cellular / Q000276:immunology; D007165:Immunosuppression Therapy / Q000379:methods; D009186:Myelin Sheath / Q000276:immunology; D009416:Nerve Regeneration / Q000276:immunology*; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D006649:Histocompatibility Antigens