NONTOLERANCE AND DIFFERENTIAL SUSCEPTIBILITY TO DIABETES IN TRANSGENIC MICE EXPRESSING MAJOR HISTOCOMPATIBILITY CLASS-II GENES ON PANCREATIC BETA-CELLS

被引:19
作者
GOTZ, J [1 ]
EIBEL, H [1 ]
KOHLER, G [1 ]
机构
[1] MAX PLANCK INST IMMUNBIOL, POSTFACH 1169, W-7800 FREIBURG, GERMANY
关键词
D O I
10.1002/eji.1830200809
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In insulin‐dependent diabetes mellitus aberrant expression of major histocompatibility complex (MHC) class II antigens might induce autoimmune destruction of insulin‐producing pancreatic β cells. Here we demonstrate that already the expression of single MHC class II chains (Eαk and Eβb) is sufficient to cause diabetes without affecting β cell morphology and cell numbers. Our transgenes interfere at least in two points of insulin production leading to a severely diabetic phenotype. In one case Eβb expression led to a 10‐30‐fold decrease of mouse insulin mRNA. In another case Eαk expression reduced insulin secretion to background levels. In addition, we also found a patchy distribution of both insulin and Eαk expression, indicating heterogeneity of the β cell population, without the concommittant development of diabetes. Although the transgenic Eαk Eβb MHC class II molecules were expressed on the surface of pancreatic β cells, the transgenic mice did not prove to be tolerant for I‐E antigen. Autoimmune reactions remained absent showing that aberrant MHC class II expression on pancreatic β cells alone is not sufficient for the development of autoimmune diabetes in mice. Copyright © 1990 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
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收藏
页码:1677 / 1683
页数:7
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