Long-term tolerance to kidney allografts in a preclinical canine model.
Durable immune tolerance supporting vascularized allotransplantation offers the possibility of extending graft survival and avoiding harmful complications of chronic immunosuppression. Immune tolerance to renal allografts was induced in a preclinical canine model through engraftment of donor hematopoietic cells using a combination of low-dose total body irradiation and a short course of immunosuppression. Subsequently, donor renal allografts were transplanted accompanied by bilateral native nephrectomies. With 5-year follow up, we found normal renal function in all recipients and no histological evidence of acute or chronic rejection. This tolerance does not extend universally to donor skin grafts, however, with two of four animals rejecting delayed donor skin grafts. Hematopoietic chimerism produces durable and robust immune tolerance to kidney allografts, although incomplete tolerance to donor skin grafting.
Kuhr
Christian S
CS
Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, Seattle, WA 98109, USA. kuhrc@u.washington.edu
Yunusov
Murad
M
Sale
George
G
Loretz
Carol
C
Storb
Rainer
R
D000818:Animals; D004285:Dogs; D006085:Graft Survival / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D007165:Immunosuppression Therapy; D007668:Kidney / Q000473:pathology / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D023421:Models, Animal; D016038:Skin Transplantation / Q000276:immunology; D013997:Time Factors; D023001:Transplantation Tolerance / Q000276:immunology*