期刊
JOURNAL OF IMMUNOLOGY
卷 182, 期 1, 页码 250-258出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.182.1.250
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资金
- Ministry of Education, Science, and Culture, Japan
- National Health and Medical Research Council of Australia Program
- Cancer Council of Victoria Project Grant
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI035021, R37AI071922] Funding Source: NIH RePORTER
Activation of invariant NKT (iNKT) cells in the liver is generally regarded as the critical step for Con A-induced hepatitis, and the role of NK cell receptors for iNKT cell activation is still controversial. In this study we show that blockade of the NKG2A-mediated inhibitory signal with antagonistic anti-NKG2A/C/E mAb (20d5) aggravated Con A-induced hepatitis in wild-type, Fas ligand (FasL)-mutant gld, and IL-4-deficient mice even with NK cell and CD8 T cell depletion, but not in perforin-, IFN-gamma-, or IFN-gamma- and perforin-deficient mice. Consistently, 20d5 pretreatment augmented serum IFN-gamma levels and perforin-dependent cytotoxicity of liver mononuclear cells following Con A injection, but not their FasL/Fas-dependent cytotoxicity. However, blockade of NKG2A-mediated signals during the cytotoxicity effector phase did not augment cytotoxic activity. Activated iNKT cells promptly disappeared after Con A injection, whereas NK1(-) iNKT cells, which preferentially expressed CD94/NKG2A, predominantly remained in the liver. Pretreatment with 20d5 appeared to facilitate disappearance of iNKT cells, particularly NK1(-) iNKT cells. Moreover, Con A-induced and a-galactosylceramide-induced hepatic injury was very severe in CD94/NKG2A-deficient DBA/2J mice compared with CD94/NKG2A-intact DBA/2JJcI mice. Overall, these results indicated that a NKG2A-mediated signal negatively regulates iNKT cell activation and hepatic injury. The Journal of Immunology, 2009, 182: 250-258.
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