Rat nigral xenografts survive in the brain of MHC class II-, but not class I-deficient mice

• Published in: Neuroscience 2002-01, Vol.115 (2), p.495-504
• Main Authors: Duan, W.-M, Westerman, M.A, Wong, G, Low, W.C
• Format: Article
• Language: English
• Subjects: Animals; dopamine; Dopamine - physiology; Graft Survival - immunology; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class II - genetics; Immunohistochemistry; immunology; major histocompatibility complex antigens; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; neural transplantation; Parkinson’s disease; Rats; Rats, Sprague-Dawley; Substantia Nigra - transplantation; T-Lymphocytes, Helper-Inducer - immunology; Transplantation, Heterologous; Tyrosine 3-Monooxygenase - analysis
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(02)00382-2

We have examined the role of the indirect pathway of antigen recognition and T cells in neural xenografts rejection by using major histocompatibility complex (MHC) class II-deficient mice as xenograft recipients. Dissociated embryonic ventral mesencephalic tissue from Sprague–Dawley rats was stereotaxically injected as a cell suspension into the striatum of MHC class II-deficient adult mice as well as MHC class I-deficient and wild-type mice as controls. All of the MHC class II-deficient mice had surviving grafts in the striatum 4 weeks post-grafting. In contrast, only a few of the MHC class I-deficient mice exhibited very small grafts and none of the wild-type mice had any surviving grafts. The mean number of surviving transplanted dopamine neurons in the MHC class II-deficient group was significantly larger than that observed in the other two groups. Moderate levels of MHC class I antigen expression were seen in the transplantation sites of some animals in the MHC class II-deficient group. No helper or cytotoxic T cells were observed infiltrating into the graft sites of this group. However, there were markedly increased levels of expression of MHC class I and class II antigens, and a number of T cells infiltrating in the graft sites in both the MHC class I-deficient and wild-type groups. These results show that rat embryonic nigral tissue can survive transplantation in the brain of the MHC class II-deficient mice for at least 4 weeks without any overt signs of rejection, suggesting that the indirect pathway of foreign antigen recognition mediated by host MHC class II molecules and helper T cells plays an important role in the rejection responses to intracerebral xenografts.