Anti-islet immunity and thymic dysfunction in the mutant diabetic C57BL/KsJ db/db mouse.
Anti-islet immune reactions were studied in vitro in genetically diabetic homozygote C57BL/KsJ db/db mice, using murine islet cells as a target. Spleen lymphocytes inhibited insulin secretion by the islet cells. This inhibition was abolished when T-cells were eliminated by treatment with anti-Thy 1.2 monoclonal antibody in the presence of complement. Anti-islet complement-dependent antibody (CDA) and antibody-dependent cell cytotoxicity (ADCC) were also found in the sera of these mice. This anti-islet immunity was detectable as early as the tenth day of life and lasted throughout the entire life span of the animals. A significant lymphopenia was detected in thymus and spleen cell populations. None of these anomalies was found in control heterozygote mice. Thymic function was explored in the same mice by evaluating their serum thymic factor (FTS) levels using a rosette assay. The age-dependent decline of FTS levels was significantly accelerated in diabetic mice as compared with heterozygous littermates. Furthermore, FTS inhibitory immunoglobulins were detected in db/db mouse sera, which inactivated in vitro the biologic potency of synthetic FTS. Histologically, the thymus displayed an accelerated involution. It was shown by indirect immunofluorescence using anti-FTS monoclonal antibodies that the number of FTS+ cells was reduced in db/db mouse thymuses. Histologic study of the islets of Langerhans showed early signs of beta-cell hyperactivity and hypertrophy, followed by beta-cell rarefaction and profound dislocation of islet architecture. Insulitis was not detected.
D000818:Animals; D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity; D001323:Autoantibodies / Q000032:analysis*; D003165:Complement System Proteins / Q000502:physiology; D003920:Diabetes Mellitus / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology*; D007958:Leukocyte Count; D008214:Lymphocytes; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology*; D008817:Mice, Mutant Strains / Q000276:immunology*; D012376:Rodent Diseases / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000473:pathology; D013935:Thymic Factor, Circulating / Q000378:metabolism; D013950:Thymus Gland / Q000473:pathology / Q000503:physiopathology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007328:Insulin; D003165:Complement System Proteins; D013935:Thymic Factor, Circulating