Effect of immunodeficiency on diabetogenesis in genetically diabetic (db/db) mice.
The pathogenesis of diabetes in C57BL/KsJ-db/db mice has been proposed to entail autoimmune mechanisms. We have combined immunodeficiency genes with the db mutation to determine whether beta cell necrosis and establishment of severe diabetes would occur in the absence of normal T and/or B lymphocyte functions. Inbred mice carrying the recessive mutations, severe combined immunodeficiency (scid), X-linked immunodeficiency (xid), nude (nu), and the Y-linked autoimmune accelerator (Yaa), were crossed with strains congenic for the db mutation. The diabetes syndrome was studied in double homozygotes produced in the F2 generation. In another experiment, C57BL/KsJ-db/db males were made T cell function deficient by adolescent thymectomy followed by lethal irradiation and bone marrow reconstitution. None of these manipulations served to prevent the induction of a severe diabetes syndrome in any of the model systems analyzed. Thus, diabetogenesis characterized by massive necrosis of the pancreatic beta cells and atrophy of the pancreatic islets was observed in both the absence of normal T cell function (as assessed by absence of T cell mitogen response) and humoral autoimmunity against beta cell antigens (insulin, retroviral p73). In conclusion, our data indicate that anti-beta cell autoimmunity is not a primary event in the etiopathogenesis of diabetes in the db/db mouse.
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D005796:Genes; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000235:genetics*; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology; D008817:Mice, Mutant Strains / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology