Antigen-specific cytotoxicity by invariant NKT cells in vivo is CD95/CD178-dependent and is correlated with antigenic potency.
Antigen-specific cytotoxicity by invariant NKT cells in vivo is CD95/CD178-dependent and is correlated with antigenic potency.
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DOI：
10.4049/jimmunol.1001018
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发表时间：
2010-09-01
期刊：
影响因子：
--
通讯作者：
Kronenberg M
中科院分区：
文献类型：
--
作者：
Wingender G;Krebs P;Beutler B;Kronenberg M
不变NKT（iNKT）细胞是T淋巴细胞的一个独特亚群，在用糖脂Ag（如模型Ag α-半乳糖神经酰胺（αGalCer））活化后迅速发挥效应子功能。许多研究已经调查了导致iNKT细胞产生Th 1和Th 2细胞因子的机制，以及这些细胞产生的大量细胞因子的作用。然而，关于iNKT细胞毒性的机制知之甚少。在这里，我们研究了抗原可用性和强度的影响，以及参与iNKT细胞毒性的分子。我们证明了iNKT细胞的体内细胞毒性与靶点表达的CD 1d的量以及TCR对靶糖脂Ag的亲和力直接相关。来自脾、肝和胸腺的iNKT细胞的体外细胞毒性相当。令人惊讶的是，我们发现iNKT细胞在体内的抗原特异性细胞毒性几乎完全依赖于CD 95（Fas）与CD 178（FasL）的相互作用，并且这种机制可以有效地用于肿瘤保护。因此，与主要依赖穿孔素/颗粒酶介导机制的NK细胞不同，iNKT细胞在体内的抗原特异性细胞毒性主要限于CD 95/CD 178途径。
Invariant NKT (iNKT) cells are a unique subset of T lymphocytes that rapidly carry out effector functions following activation with glycolipid Ags, such as the model Ag α-galactosylceramide (αGalCer). Numerous studies have investigated the mechanisms leading to Th1- and Th2 cytokine production by iNKT cells, and the effects of the copious amounts of cytokines these cells produce. Less is known, however, about the mechanisms of iNKT cell cytotoxicity. Here we investigated the effect of antigen availability and strength, as well as the molecules involved in iNKT cytotoxicity. We demonstrate that the iNKT cell cytotoxicity in vivo correlates directly with the amount of CD1d expressed by the targets as well as the TCR affinity for the target glycolipid Ag. iNKT cells from spleen, liver and thymus were comparable in their cytotoxicity in vitro. Surprisingly, we show that the antigen-specific cytotoxicity of iNKT cells in vivo depended almost exclusively on the interaction of CD95 (Fas) with CD178 (FasL), and that this mechanism can be efficiently utilized for tumor protection. Therefore unlike NK cells, which rely mostly on perforin/granzyme mediated mechanisms, the antigen-specific cytotoxicity of iNKT cells in vivo is largely restricted to the CD95/CD178 pathway.
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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
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15.3
作者：
Brossay, L;Chioda, M;Burdin, N;Koezuka, Y;Casorati, G;Dellabona, P;Kronenberg, M
通讯作者：
Kronenberg, M