PMID- 9185663 OWN - NLM STAT- MEDLINE DCOM- 19970728 LR - 20171116 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 48 IP - 5 DP - 1997 Jun 1 TI - Treatment of rat hemiparkinson model with xenogeneic neural transplantation: tolerance induction by anti-T-cell antibodies. PG - 385-96 AB - To obtain basic knowledge for the application of xenogeneic neural transplantation to patients with Parkinson's disease, the rejection process of xenogeneic neural grafts in rats was examined and a therapy to control it was developed. Tissues including the ventral mesencephalon were taken from mouse embryos and transplanted into the right lateral ventricle of mature male rats. Transplanted xenografts were usually rejected by day 15. To prevent the graft rejection, host rats were treated with anti-T-cell receptor alphabeta (anti-TCR alphabeta) or anti-CD2 monoclonal antibody (mAb) or by a combination of the two. Anti-TCR alphabeta (1 mg/kg) and anti-CD2 (7 mg/kg) mAb were administered for 3 consecutive days (day -2, -1, and 0 of transplantation). Although the administration of mAb against either CD2 or TCR alphabeta did not induce tolerance, the combination therapy with anti-CD2 and anti-TCR alphabeta mAb produced graft survival for more than 100 days. The tolerance induced by this combined antibody therapy is antigen specific because rats with long-term surviving neural xenograft accepted a second neural graft from the same donor strain C3H/He mouse, but not from a third-party strain BALB/c mouse, without additional treatment. In addition, T cells isolated from these rats did not respond to cultured C3H/He brain cells, but did respond vigorously to BALB/c brain cells in mixed lymphocyte reaction. More importantly, the finding that xenograft transplantation with the proper treatment reduced the rotation rate of 6-OHDA-lesioned rats confirmed that surviving grafts functioned properly. The results of the present study suggest that xenogeneic neural transplantation in combination with T-cell-targeted immunotherapy is an effective approach for treatment of Parkinson's disease. FAU - Okura, Y AU - Okura Y AD - Department of Neurosurgery, Brain Research Institute, Niigata University, Japan. FAU - Tanaka, R AU - Tanaka R FAU - Ono, K AU - Ono K FAU - Yoshida, S AU - Yoshida S FAU - Tanuma, N AU - Tanuma N FAU - Matsumoto, Y AU - Matsumoto Y LA - eng PT - Journal Article PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Antibodies, Monoclonal) RN - 0 (CD2 Antigens) RN - 0 (Receptors, Antigen, T-Cell) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) SB - IM MH - Animals MH - Antibodies, Monoclonal/*pharmacology MH - Brain Tissue Transplantation/*immunology MH - CD2 Antigens/immunology MH - Cerebral Ventricles/surgery MH - Graft Rejection/immunology MH - Graft Survival/immunology MH - Immune Tolerance/immunology MH - Immunohistochemistry MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C3H MH - Neurons/enzymology/immunology/transplantation MH - Parkinson Disease, Secondary/*surgery MH - Rats MH - Rats, Inbred F344 MH - Receptors, Antigen, T-Cell/*immunology MH - Transplantation, Heterologous/*immunology MH - Tyrosine 3-Monooxygenase/analysis EDAT- 1997/06/01 00:00 MHDA- 2000/06/20 09:00 CRDT- 1997/06/01 00:00 PHST- 1997/06/01 00:00 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1997/06/01 00:00 [entrez] AID - 10.1002/(SICI)1097-4547(19970601)48:5<385::AID-JNR1>3.0.CO;2-A [pii] PST - ppublish SO - J Neurosci Res. 1997 Jun 1;48(5):385-96.