期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 4, 页码 1210-1215出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1118834109
关键词
virus persistence; effector T cells; virus elimination; NK cell activation; regulatory innate immunity
资金
- Canadian Institute for Health Research [CIHR-MOP-106529]
- Alexander von Humboldt Foundation [SKA2008, SKA2010]
- Deutsche Forschungsgemeinschaft [LA1419/3-1]
- Heinrich Heine University
- Collaborative Research Center [SFB575]
- Swiss National Science Foundation/Swiss Foundation for Medical-Biological Scholarships [PASMP3-127678/1]
- Ontario Ministry of Health and Long-Term Care
Infections with HIV, hepatitis B virus, and hepatitis C virus can turn into chronic infections, which currently affect more than 500 million patients worldwide. It is generally thought that virus-mediated T-cell exhaustion limits T-cell function, thus promoting chronic disease. Here we demonstrate that natural killer (NK) cells have a negative impact on the development of T-cell immunity by using the murine lymphocytic choriomeningitis virus. NK cell-deficient (Nfil3(-/-), E4BP4(-/-)) mice exhibited a higher virus-specific T-cell response. In addition, NK cell depletion caused enhanced T-cell immunity in WT mice, which led to rapid virus control and prevented chronic infection in lymphocytic choriomeningitis virus clone 13- and reduced viral load in DOCILE-infected animals. Further experiments showed that NKG2D triggered regulatory NK cell functions, which were mediated by perforin, and limited T-cell responses. Therefore, we identified an important role of regulatory NK cells in limiting T-cell immunity during virus infection.
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