Prevention of type I diabetes in nonobese diabetic mice by allogenic bone marrow transplantation.
An animal model [the nonobese diabetic (NOD) mouse] for type I diabetes features a striking infiltration of T cells into the pancreatic islets. This infiltration selectively destroys beta cells. Most of the T cells are Lyt-1+, but some are Lyt-2+,3+. Transfer experiments using parabiosis revealed that insulitis can be transferred within 2 weeks after parabiosis to immunoincompetent thymectomized mice. When NOD mice (6 mo old) were irradiated and reconstituted with bone marrow cells from young BALB/c nu/nu mice (less than 2 mo old), the NOD mice exhibited neither insulitis nor overt diabetes. Deposits of immunoglobulin in mesangial areas of the glomeruli disappeared within 3 mo after bone marrow transplantation in such irradiated allogeneic bone marrow reconstituted mice. Assays for immunological functions, including mitogen response and mixed lymphocyte reaction, revealed that both T- and B-cell functions were increased in NOD mice with overt diabetes. NOD mice reconstituted with BALB/c nu/nu bone marrow cells displayed normal T- and B-cell functions. The newly developed T cells in the allogeneic bone marrow recipients are tolerant to cells with both donor- and host-type major histocompatibility complex determinants. These results suggest that bone marrow transplantation may ultimately be developed as a component of a strategy to be employed for treatment of type I diabetes in humans.
D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy; D016026:Bone Marrow Transplantation; D003601:Cytotoxicity Tests, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005455:Fluorescent Antibody Technique; D005951:Glucose Tolerance Test; D007515:Islets of Langerhans / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D014184:Transplantation, Homologous