title: Implantation of xenografts into the parkinsonian rat brain after portal venous administration of xenogeneic donor spleen cells.
abstract: OBJECTIVE
  The purpose of the present study was to examine the effect of pretransplantation portal venous immunization with ultraviolet B (UVB)-treated donor spleen cells on neural xenograft transplantation.
  
  
  METHODS
  Cells from a murine catecholaminergic cell line derived from the B6/D2 F1 mouse, CATH.a, were used as a xenograft. Thirty hemiparkinsonian rats were divided into three different treatment groups. Group 1 received saline in the dopamine-denervated striatum; Group 2 received xenograft cells; and Group 3 received portal venous administration of UVB-irradiated B6/D2 F1 splenocytes 7 days before receiving xenograft cells. Xenograft function was determined by reviewing apomorphine-induced rotation at 2-week intervals, and xenograft survival was examined at 4 and 12 weeks after transplantation by immunohistochemical staining for murine tyrosine hydroxylase (THase). Rotational behavior was improved in both xenograft-transplanted groups (Groups 2 and 3); however, the animals in Group 3 displayed a significantly reduced rotational behavior compared with Group 2. In Group 2, many inflammatory cells and a few THase-positive cells were found at the graft sites 4 weeks after transplantation. In Group 3, however, a large number of THase-positive cells were found with few inflammatory cells. The THase-positive cells disappeared in the Group 2 rats at 12 weeks, but remained in Group 3 animals. In Group 3 rats proliferation of spleen cells in a mixed lymphocyte reaction was suppressed in a donor-specific fashion.
  
  
  CONCLUSIONS
  This work demonstrates improved neural xenograft survival and function by pretransplantation portal venous immunization with UVB-irradiated xenogeneic donor splenocytes. On the basis of these findings, the authors suggest the possibility of creating donor-specific immunological tolerance in the brain by administration of xenogeneic donor lymphocytes via the portal vein.
authors.affiliation: Department of Neurosurgery and Parasitology, Nara Medical University, Kashihara, Japan. hitake@nmu-gw.naramed-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Takeuchi
authors.forename: M
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: S
authors.initials: S
authors.lastname: Kanda
authors.forename: M
authors.initials: M
authors.lastname: Nonaka
authors.forename: F
authors.initials: F
authors.lastname: Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Ishizaka
authors.forename: T
authors.initials: T
authors.lastname: Sakaki
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001932:Brain Neoplasms; D002455:Cell Division; D018920:Coculture Techniques; D004298:Dopamine / Q000096:biosynthesis; D005260:Female; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy / Q000379:methods; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008809:Mice, Inbred C3H; D009474:Neurons / Q000201:enzymology / Q000637:transplantation*; D020734:Parkinsonian Disorders / Q000601:surgery*; D011169:Portal Vein; D051381:Rats; D011916:Rats, Inbred F344; D012399:Rotation; D013154:Spleen / Q000166:cytology* / Q000528:radiation effects; D014183:Transplantation, Heterologous / Q000276:immunology / Q000379:methods*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000637:transplantation; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D014466:Ultraviolet Rays
chemical_list: D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine