NKG2A inhibits invariant NKT cell activation in hepatic injury.
NKG2A inhibits invariant NKT cell activation in hepatic injury.
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DOI：
10.4049/jimmunol.182.1.250
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Smyth MJ
中科院分区：
文献类型：
--
作者：
Kawamura T;Takeda K;Kaneda H;Matsumoto H;Hayakawa Y;Raulet DH;Ikarashi Y;Kronenberg M;Yagita H;Kinoshita K;Abo T;Okumura K;Smyth MJ
肝脏中不变性NKT （iNKT）细胞的激活通常被认为是cona诱导肝炎的关键步骤，NK细胞受体在iNKT细胞激活中的作用仍然存在争议。在这里，我们发现用拮抗nkg2a /C/E单抗（20d5）阻断nkg2a介导的抑制信号会加重Con - a诱导的肝炎，在野生型、Fas配体（FasL）突变型金和il -4缺陷小鼠中，即使NK细胞和CD8 T细胞耗竭，但在穿孔素-、IFN-γ-或IFN-γ-和穿孔素缺陷小鼠中则不会。与此一致的是，20d5预处理增强了Con A注射后肝单个核细胞的血清IFN-γ水平和穿孔素依赖性细胞毒性，但不增强其FasL/ fas依赖性细胞毒性。然而，在细胞毒性效应期阻断nkg2a介导的信号并不会增加细胞毒性活性。注射Con A后，活化的iNKT细胞迅速消失，而优先表达CD94/NKG2A的NK1−iNKT细胞主要留在肝脏中。20d5预处理可以促进iNKT细胞，尤其是NK1−iNKT细胞的消失。与CD94/ nkg2a完整的DBA/2JJcl小鼠相比，Con a诱导的和α-半乳糖神经酰胺诱导的CD94/ nkg2a缺失小鼠的肝损伤非常严重。总之，这些结果表明nkg2a介导的信号负调控iNKT细胞活化和肝损伤。
Activation of invariant NKT (iNKT) cells in the liver is generally regarded as the critical step for concanavallin A (Con A)-induced hepatitis, and the role of NK cell receptors for iNKT cell activation is still controversial. Here 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-γ-, or IFN-γ- and perforin-deficient mice. Consistently, 20d5 pre-treatment augmented serum IFN-γ 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, while NK1− iNKT cells, that preferentially expressed CD94/NKG2A, predominantly remained in the liver. Pre-treatment with 20d5 appeared to facilitate disappearance of iNKT cell, particularly NK1− iNKT cells. Moreover, Con A-induced and α-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 NKG2A-mediated signal negatively regulates iNKT cell activation and hepatic injury.
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DOI：
10.1084/jem.192.5.741
发表时间：
2000-09-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Matsuda JL;Naidenko OV;Gapin L;Nakayama T;Taniguchi M;Wang CR;Koezuka Y;Kronenberg M
通讯作者：
Kronenberg M
DOI：
10.1084/jem.179.5.1529
发表时间：
1994-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mizuhara H;O'Neill E;Seki N;Ogawa T;Kusunoki C;Otsuka K;Satoh S;Niwa M;Senoh H;Fujiwara H
通讯作者：
Fujiwara H
影响因子：
15.3
作者：
Kaneko, Y;Harada, M;Kawano, T;Yamashita, M;Shibata, Y;Gejyo, F;Nakayama, T;Taniguchi, M
通讯作者：
Taniguchi, M
影响因子：
4.4
作者：
Maeda, M;Lohwasser, S;Takei, F
通讯作者：
Takei, F
影响因子：
13.5
作者：
Nicoletti, F;Di Marco, R;Meroni, P
通讯作者：
Meroni, P