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NKG2A inhibits invariant NKT cell activation in hepatic injury.
J Immunol ; 182(1): 250-8, 2009 Jan 01.
Article em En | MEDLINE | ID: mdl-19109156
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 alpha-galactosylceramide-induced hepatic injury was very severe in CD94/NKG2A-deficient DBA/2J mice compared with CD94/NKG2A-intact DBA/2JJcl mice. Overall, these results indicated that a NKG2A-mediated signal negatively regulates iNKT cell activation and hepatic injury.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ativação Linfocitária / Células T Matadoras Naturais / Subfamília C de Receptores Semelhantes a Lectina de Células NK / Doença Hepática Induzida por Substâncias e Drogas / Inibidores do Crescimento Limite: Animals Idioma: En Revista: J Immunol Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ativação Linfocitária / Células T Matadoras Naturais / Subfamília C de Receptores Semelhantes a Lectina de Células NK / Doença Hepática Induzida por Substâncias e Drogas / Inibidores do Crescimento Limite: Animals Idioma: En Revista: J Immunol Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Japão