Prevention of both rejection and recurrence of autoimmune disease in the NOD/Lt mouse following segmental pancreas transplantation.
In the NOD/Lt recipient mice, disease recurrence in untreated isografts was extremely rapid (median less than 10 days) compared to the rejection of an untreated BALB/c pancreas graft in a CBA mouse (median 26 days). This would be expected since disease recurrence is a secondary response in diabetic mice with lymphocytes primed to respond to the beta-cell autoantigen. The median survival time for the untreated CBA to NOD/Lt pancreas graft falls, as expected, between these two survival times (median 20 days). Although anti-CD4 and/or anti-CD8 were effective in delaying or stopping autoimmune disease recurrence and rejection in the separate models, they were unsuccessful in significantly altering survival times in the combined model, despite using 2-mg doses and dual therapy. Similar doses of anti-CD4 have failed to prevent islet allograft rejection in NOD/Lt mice. Long-term dual treatment may be required to inactivate CD4+ and CD8+ T cells in the NOD/Lt mouse to prevent both autoimmune disease recurrence and rejection. NOD/Lt recipients will require greater immunosuppression to prevent rejection-autoimmune disease recurrence will be easier to prevent. This study shows the value of using NOD/Lt mice, with naturally occurring type 1 diabetes, for assessment of immunosuppressive therapy to prevent failure of pancreas transplants.
Purcell
L J
LJ
Department of Surgery, Royal Melbourne Hospital, Parkville, Australia.
Mottram
P L
PL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D006084:Graft Rejection / Q000517:prevention & control; D007165:Immunosuppression Therapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD; D016035:Pancreas Transplantation / Q000276:immunology*; D013154:Spleen / Q000637:transplantation
D000911:Antibodies, Monoclonal