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

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...

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Bibliographic Details
Published in:	Science (American Association for the Advancement of Science) 1990-07, Vol.249 (4966), p.293-295
Main Authors:	Böhme, Jan, Schuhbaur, Brigitte, Kanagawa, Osami, Benoist, Christophe, Mathis, Diane
Format:	Article
Language:	eng
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 Islets of Langerhans - immunology Major Histocompatibility Complex Medical genetics Medical immunity 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
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Summary:	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.
ISSN:	0036-8075 1095-9203