MHC-Linked Protection from Diabetes Dissociated from Clonal Deletion of T Cells

• Published in: Science (American Association for the Advancement of Science) Vol. 249; no. 4966; pp. 293 - 295
• Main Authors: Böhme, Jan, Schuhbaur, Brigitte, Kanagawa, Osami, Benoist, Christophe, Mathis, Diane
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 20.07.1990; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Autoimmune diseases; Biological and medical sciences; Causes of; Clonal deletion; Clone Cells; Crosses, Genetic; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - prevention & control; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Genes, MHC Class II; Genetic aspects; Genetics; Histocompatibility antigens; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; HLA antigens; HLA histocompatibility antigens; Immunity (Disease); Islets of Langerhans - immunology; Major Histocompatibility Complex; Medical genetics; Medical research; Medical sciences; Mice; Mice, Mutant Strains; Mice, Transgenic; Molecules; Mutation; Promoter Regions, Genetic; Receptors, Antigen, T-Cell - genetics; T lymphocytes; T-Lymphocytes - immunology; Thymus Gland - immunology; Transgenes; Transgenic animals; Type 1 diabetes mellitus; Prevention; Vertebrata; Mammalia; Gene; Mouse; Animal; Diabetes mellitus; Major histocompatibility system; Rodentia
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2115690

The I-E molecule of the major histocompatibility complex (MHC) can prevent the spontaneous development of diabetes in nonobese diabetic (NOD) mice. The mechanism of this protection has been investigated by breeding wild-type and promotermutated E$^k_\alpha$ transgenes onto the NOD genetic background. Animals carrying the various mutated transgenes expressed I-E on different subsets of immunocompetent cells, and thus cells important for the I-E protective effect could be identified. Although the wild-type transgene prevented the infiltration of lymphocytes into pancreatic islets, none of the mutants did. However, all of the transgenes could mediate the intrathymic elimination of T cells bearing antigen receptors with variable regions that recognize I-E. Thus, the I-E molecule does not protect NOD mice from diabetes simply by inducing the deletion of self-reactive T cells.