Transplantation tolerance and autoimmunity after xenogeneic thymus transplantation.
Successful grafting of vascularized xenografts (Xgs) depends on the ability to reliably induce both T cell-independent and -dependent immune tolerance. After temporary NK cell depletion, B cell suppression, and pretransplant infusion of donor Ags, athymic rats simultaneously transplanted with hamster heart and thymus Xgs developed immunocompetent rat-derived T cells that tolerated the hamster Xgs but provoked multiple-organ autoimmunity. The autoimmune syndrome was probably due to an insufficient development of tolerance for some rat organs; for example, it led to thyroiditis in the recipient rat thyroid, but not in simultaneously transplanted donor hamster thyroid. Moreover, grafting a mixed hamster/rat thymic epithelial cell graft could prevent the autoimmune syndrome. These experiments indicate that host-type thymic epithelial cells may be essential for the establishment of complete self-tolerance and that mixed host/donor thymus grafts may induce T cell xenotolerance while maintaining self-tolerance in the recipient.
Xia
G
G
Laboratory for Experimental Transplantation, University of Leuven, Leuven, Belgium.
Goebels
J
J
Rutgeerts
O
O
Vandeputte
M
M
Waer
M
M
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006224:Cricetinae; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005333:Fetus / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011923:Rats, Nude; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000196:embryology / Q000473:pathology / Q000637:transplantation*; D023001:Transplantation Tolerance / Q000235:genetics; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology; D014184:Transplantation, Homologous