Complete prevention of diabetes in transgenic NOD mice expressing I-E molecules

• Published in: Immunology letters Vol. 31; no. 1; pp. 47 - 52
• Main Authors: Uno, Masashi, Miyazaki, Toru, Uehira, Masahiro, Nishimoto, Hirofumi, Kimoto, Masao, Miyazaki, Junichi, Yamamura, Ken-ichi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 1992; Elsevier
• Subjects: Animals; Animals, Genetically Modified; Biological and medical sciences; Diabetes Mellitus, Type 1 - prevention & control; Experimental and animal immunopathology. Animal models; Gene Expression; Genetic Therapy; Histocompatibility Antigens Class II - genetics; Immunopathology; Insulitis; Islets of Langerhans - pathology; Lymphocytes - physiology; Medical sciences; MHC class II; Mice; Mice, Mutant Strains; Monocytes - physiology; Transgenic mouse; Insulitis; NOD-E α d; MMC; NOD; TdR; Transgenic mouse; GL-Phe; MHC; MHC class II; mAb; IFN; B6-E α d; MLR; PBL; Endocrinopathy; Immunopathology; Animal model; Mixed lymphocyte reaction; Pathogenesis; Major histocompatibility system; Rodentia; Class II histocompatibility antigen; Transgenic animal; Gene expression; H-2-System; Characterization; Resistance; Vertebrata; Mammalia; Mouse; Insulin dependent diabetes
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/0165-2478(92)90009-D

Previously, we showed that transgenic expression of the MHC (major histocompatibility complex) class II I-E molecules prevented insulitis in non-obese diabetic (NOD) mice at the age of 19 weeks. To rule out the possibility that the I-E expression merely delays the onset of insulitis, we have further characterized the expression and function of the I-E molecule expressed in transgenic NOD mice and confirmed our previous observations. Northern blot analysis showed that the transgenic E α d gene was expressed in a pattern similar to the endogenous E α d gene in BALB/c mice. The newly expressed I-E molecules were recognized as an alloantigen by the T lymphocytes of normal NOD mice as shown by mixed lymphocyte reaction (MLR). Transgenic NOD mice were resistant to the treatment by cyclophosphamide, which effectively induces diabetes in normal NOD mice, and did not develop diabetes up to 40 weeks of age. On the basis of these findings, we discuss the role of I-E molecules in the prevention of diabetes in NOD mice.