Rat nigral xenografts survive in the brain of MHC class II-, but not class I-deficient mice.
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.
Duan
W-M
WM
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis 55455, USA.
Westerman
M A
MA
Wong
G
G
Low
W C
WC
D000818:Animals; D004298:Dopamine / Q000502:physiology; D006085:Graft Survival / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000637:transplantation*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014183:Transplantation, Heterologous; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine