NONIMMUNE THYROID DESTRUCTION RESULTS FROM TRANSGENIC OVEREXPRESSION OF AN ALLOGENEIC MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I PROTEIN
- Author(s)
- FRAUMAN, AG; CHU, P; Harrison, LC;
- Details
- Publication Year 1993-03,Volume 13,Issue #3,Page 1554-1564
- Journal Title
- MOLECULAR AND CELLULAR BIOLOGY
- Publication Type
- Journal Article
- Abstract
- The overexpression of major histocompatibility complex (MHC) class I molecules in endocrine epithelial cells is an early feature of autoimmune thyroid disease and insulin-dependent diabetes mellitus, which may reflect a cellular response, e.g., to viruses or toxins. Evidence from a transgenic model in pancreatic beta cells suggests that MHC class I overexpression could play an independent role in endocrine cell destruction. We demonstrate in this study that the transgenic overexpression of an allogeneic MHC class I protein (H-2K(b)) linked to the rat thyroglobulin promoter, in H-2K(k) mice homozygous for the transgene, leads to thyrocyte atrophy, hypothyroidism, growth retardation, and death. Thyrocyte atrophy occurred in the absence of lymphocytic infiltration. Tolerance to allogeneic class I was revealed by the reduced ability of primed lymphocytes from transgenic mice to lyse H-2K(b) target cells in vitro. This nonimmune form of thyrocyte destruction and hypothyroidism recapitulates the beta-cell destruction and diabetes that results from transgenic overexpression of MHC class I molecules in pancreatic beta cells. Thus, we conclude that overexpression of MHC class I molecules may be a general mechanism that directly impairs endocrine epithelial cell viability.
- Publisher
- AMER SOC MICROBIOLOGY
- Keywords
- PANCREATIC BETA-CELLS; TUMOR-NECROSIS-FACTOR; DEPENDENT DIABETES-MELLITUS; HLA CLASS-II; INTERFERON-GAMMA; FACTOR-ALPHA; ABERRANT EXPRESSION; REOVIRUS INFECTION; EPITHELIAL-CELLS; GRAVES-DISEASE
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Creation Date: 1993-03-01 12:00:00