Transplanted MHC class I-deficient nonobese diabetic mouse islets are protected from autoimmune injury in diabetic nonobese recipients.
The injury of transplanted islets may occur by both autoimmune and alloimmune processes directed against MHC targets. To examine the role of MHC class I in islet graft injury, we transplanted syngeneic and allogeneic beta2-microglobulin-deficient islets into diabetic nonobese diabetic (NOD) mice. Loss of graft function was observed within 14 days using allogeneic C57BL/6 and BALB/c MHC class I deficient as well as wild-type MHC class I-bearing NOD donor islets. However, islets isolated from MHC class I-deficient NOD mice (NOD-B2 m-/-) survived indefinitely when transplanted under the kidney capsule of diabetic NOD recipients. Transplanted NOD-B2 m-/- islets were surrounded by a nondestructive periinsular infiltrate that expressed interleukin-4 in addition to interferon-gamma. These studies demonstrate the primary role of MHC class I molecules in causing autoimmune destruction or recurrent diabetes in transplanted islets.
Prange
S
S
Department of Microbiology & Immunology, University of Western Ontario, London Health Sciences Centre and the John P. Robarts Research Institute, Canada.
Zucker
P
P
Jevnikar
A M
AM
Singh
B
B
D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006085:Graft Survival; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
D015395:Histocompatibility Antigens Class I; D015847:Interleukin-4; D007371:Interferon-gamma