Interferon-gamma impacts at multiple points during the progression of autoimmune diabetes

被引:174
作者
Wang, B
Andre, I
Gonzalez, A
Katz, JD
Aguet, M
Benoist, C
Mathis, D
机构
[1] UNIV STRASBOURG 1,CNRS,INSERM,INST GENET & BIOL MOL & CELLULAIRE,F-67404 ILLKIRCH GRAFFENS,FRANCE
[2] LUDWIG INST CANC RES,CH-1066 EPALINGES,SWITZERLAND
关键词
nonobese diabetic mice; knock-out mice; autoimmune disease; cytokine;
D O I
10.1073/pnas.94.25.13844
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The role of interferon-gamma in autoimmune diabetes was assessed by breeding a null mutation of the interferon-gamma receptor of chain into the nonobese diabetic mouse strain, as well as into a simplified T cell receptor transgenic model of diabetes. In contrast to a previous report on abrogation of the interferon-gamma gene, mutation of the gene encoding its receptor led to drastic effects on disease in both mouse lines. Nonobese diabetic mice showed a marked inhibition of insulitis-both the kinetics and penetrance-and no signs of diabetes; the transgenic model exhibited near-normal insulitis, but this never evolved into diabetes, either spontaneously or after experimental provocation. This failure could not be explained by perturbations in the ratio of T helper cell phenotypes; rather, it reflected a defect in antigen-presenting cells or in the islet beta cell targets.
引用
收藏
页码:13844 / 13849
页数:6
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