Triple immunosuppression protects murine intracerebral, hippocampal xenografts in adult rat hosts: effects on cellular infiltration, major histocompatibility complex antigen induction and blood-brain barrier leakage.
Recently we reported protection of intracerebral mouse to rat hippocampal xenografts upon treatment with a combination of cyclosporin A, prednisolone and azathioprine. These findings are now supported in an extended analysis of graft-infiltrating cells. Host T-cell and macrophage infiltration and the immunocytochemical level of cellular expression of major histocompatibility complex class I and II antigens, measured by densitometric analysis, were compared between recipient rats receiving cyclosporin A alone or cyclosporin A in combination with prednisolone and azathioprine. The combination therapy resulted in a much improved survival of the xenografted hippocampal tissue with preservation of organotypic granule and pyramidal cell layers. Graft infiltration by T-cells and macrophages was significantly lower and the level of major histocompatibility complex class I and II antigen expression by the infiltrating cells markedly reduced. Lower expression of donor-type major histocompatibility complex class I antigen was also found in the xenografts in the trimedicated recipients, together with reduced blood brain barrier leakage and astrogliosis at the host-graft interface. The results demonstrate the benefits of using combined immunosuppressive strategies for protection of histoincompatible brain xenografts in the central nervous system.
Pedersen
E B
EB
Department of Anatomy and Cell Biology, University of Odense, Odense C, Denmark.
Zimmer
J
J
Finsen
B
B
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D016380:Brain Tissue Transplantation / Q000276:immunology / Q000502:physiology*; D017690:Cell Transplantation / Q000502:physiology; D003720:Densitometry; D005911:Gliosis / Q000473:pathology; D006624:Hippocampus / Q000166:cytology / Q000637:transplantation*; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D007962:Leukocytes / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D009836:Oligodendroglia / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014183:Transplantation, Heterologous / Q000276:immunology / Q000502:physiology*
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D017493:Leukocyte Common Antigens