An Abd transgene prevents diabetes in nonobese diabetic mice by inducing regulatory T cells.
AUTOR(ES)
Singer, S M
RESUMO
Susceptibility to the human autoimmune disease insulin-dependent diabetes mellitus is strongly associated with particular haplotypes of the major histocompatibility complex (MHC). Similarly, in a spontaneous animal model of this disease, the nonobese diabetic (NOD) mouse, the genes of the MHC play an important role in the development of diabetes. We have produced transgenic NOD mice that express the class II MHC molecule I-Ad in addition to the endogenous I-Ag7 molecules in order to study the role of these molecules in the disease process. Although the inflammatory lesions within the islets of Langerhans in the pancreas appear similar in transgenic and nontransgenic animals, transgenic mice develop diabetes with greatly diminished frequency compared to their nontransgenic littermates (10% of transgenic females by 30 weeks of age compared to 45% of nontransgenic females). Furthermore, adoptive transfer experiments show that T cells present in the transgenic mice are able to interfere with the diabetogenic process caused by T cells from nontransgenic mice. Thus, the mechanism by which I-Ad molecules protect mice from diabetes includes selecting in the thymus and/or inducing in the periphery T cells capable of inhibiting diabetes development.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=47610Documentos Relacionados
- Prevention of diabetes in nonobese diabetic mice by anti-I-A monoclonal antibodies: transfer of protection by splenic T cells.
- Prevention of diabetes in nonobese diabetic mice by dendritic cell transfer.
- Insulin Receptor Substrate-2 in β-Cells Decreases Diabetes in Nonobese Diabetic Mice
- Autoreactivity of T cells from nonobese diabetic mice: An I-Ag7-dependent reaction
- Suppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin.