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Science 20 July 1990:
Vol. 249. no. 4966, pp. 293 - 295
DOI: 10.1126/science.2115690
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Articles

Science, Vol 249, Issue 4966, 293-295
Copyright © 1990 by American Association for the Advancement of Science

articles

MHC-linked protection from diabetes dissociated from clonal deletion of T cells

J Bohme, B Schuhbaur, O Kanagawa, C Benoist, and D Mathis

Laboratoire de Genetique Moleculaire des Eucaryotes du CNRS, Faculte de Medecine, Strasbourg, France.

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 promoter-mutated E kappa 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.


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