Ly49D Engagement on T Lymphocytes Induces TCR-Independent Activation and CD8 Effector Functions That Control Tumor Growth
Ly49D Engagement on T Lymphocytes Induces TCR-Independent Activation and CD8 Effector Functions That Control Tumor Growth
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DOI：
10.4049/jimmunol.182.1.183
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发表时间：
2009-01-01
影响因子：
4.4
通讯作者：
MacDonald, H. Robson
中科院分区：
文献类型：
--
作者：
Merck, Estelle;Voyle, Roger B.;MacDonald, H. Robson
最近的数据显示，传统的T淋巴细胞表达的激活INK受体（NKR）提出了一个问题，他们的作用，在触发TCR非依赖性反应，可能是有害的主机。表达活化受体Ly 49 D/DAP 12的转基因小鼠提供了更好地理解ITAM信号传导在T细胞生物学中的相关性的机会。体外实验表明，Ly 49 D通过中国仓鼠卵巢（CHO）细胞表达的同源MHC I类配体或特异性Ab与T淋巴细胞的结合引发了CD 4和CD 8群体的细胞活化，并调节了活化标志物和细胞因子的产生。ITAM信号传导链DAP 12的强制表达对于Ly 49 D转基因T细胞活化是必需的。此外，Ly 49 D刺激诱导T淋巴细胞增殖，其对于CD 8 T细胞强得多。抗Ly 49 D刺激的CD 8 T细胞的表型分析及其产生高水平IFN-γ和杀死靶细胞的能力表明Ly 49 D连接产生效应细胞毒性CD 8 T细胞。Ly 49 D本身的接合也触发了活化的CD 8 T细胞的细胞毒性活性。连续转移实验证实，Ly 49 D转基因CD 8 T细胞能够控制CHO肿瘤细胞或转染Hm 1-C4（通常由CHO表达的Ly 49 D配体）的RMA细胞的生长。总之，T细胞上的Ly 49 D接合导致T细胞活化和CD 8 T细胞的全范围的TCR非依赖性效应子功能。免疫学杂志，2009，182：183-192.
Recent data showing expression of activating INK receptors (NKR) by conventional T lymphocytes raise the question of their role in the triggering of TCR-independent responses that could be damaging for the host. Transgenic mice expressing the activating receptor Ly49D/DAP12 offer the opportunity to better understand the relevance of ITAM signaling in the biology of T cells. In vitro experiments showed that Ly49D engagement on T lymphocytes by a cognate MHC class I ligand expressed by Chinese hamster ovary (CHO) cells or by specific Ab triggered cellular activation of both CD4 and CD8 populations with modulation of activation markers and cytokine production. The forced expression of the ITAM signaling chain DAP12 is mandatory for Ly49D-transgenic T cell activation. In addition, Ly49D stimulation induced T lymphocyte proliferation, which was much stronger for CD8 T cells. Phenotypic analysis of anti-Ly49D-stimulated CD8 T cells and their ability to produce high levels of IFN-gamma and to kill target cells indicate that Ly49D ligation generates effector cytotoxic CD8 T cells. Ly49D engagement by itself also triggered cytotoxic activity of activated CD8 T cells. Adoptive transfer experiments confirmed that Ly49D-transgenic CD8 T cells are able to control growth of CHO tumor cells or RMA cells transfected with Hm1-C4, the Ly49D ligand normally expressed by CHO. In conclusion, Ly49D engagement on T cells leads to T cell activation and to a full range of TCR-independent effector functions of CD8 T cells. The Journal of Immunology, 2009, 182: 183-192.