Target cell defense prevents the development of diabetes after viral infection

被引:175
作者
Flodström, M
Maday, A
Balakrishna, D
Cleary, MM
Yoshimura, A
Sarvetnick, N
机构
[1] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[2] Kyushu Univ, Med Inst Bioregulat, Higashi Ku, Fukuoka 8128582, Japan
关键词
D O I
10.1038/ni771
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The mechanisms that regulate susceptibility to virus-induced autoimmunity remain undefined. We establish here a fundamental link between the responsiveness of target pancreatic beta cells to interferons (IFNs) and prevention of coxsackievirus B4 ( CVB4)-induced diabetes. We found that an intact beta cell response to IFNs was critical in preventing disease in infected hosts. The antiviral defense, raised by beta cells in response to IFNs, resulted in a reduced permissiveness to infection and subsequent natural killer (NK) cell dependent death. These results show that beta cell defenses are critical for beta cell survival during CVB4 infection and suggest an important role for IFNs in preserving NK cell tolerance to beta cells during viral infection. Thus, alterations in target cell defenses can critically influence susceptibility to disease.
引用
收藏
页码:373 / 382
页数:10
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