Cancer Immunology, Peter MacCallum Cancer Centre, East Melbourne 3002, Victoria, Australia;
J Immunol. 2014 Jan 15;192(2):553-7. doi: 10.4049/jimmunol.1302197. Epub 2013 Dec 13.
DNAX accessory molecule 1 (DNAM-1) is expressed on all CD8(+) T cells and promotes their activation and effector function. DNAM-1 interacts with LFA-1, a critical molecule for immunological synapse formation between T cells and APCs, and for cytotoxic killing of target cells. Mice that lack DNAM-1 display abnormal T cell responses and antitumor activity; however, the mechanism involved is unclear. In this article, we show that DNAM-1 deficiency results in reduced proliferation of CD8(+) T cells after Ag presentation and impaired cytotoxic activity. We also demonstrate that DNAM-1-deficient T cells show reduced conjugations with tumor cells and decreased recruitment of both LFA-1 and lipid rafts to the immunological synapse, which correlates with reduced tumor cell killing in vitro. This synapse defect may explain why DNAM-1-deficient mice cannot clear tumors in vivo, and highlights the importance of DNAM-1 and the immunological synapse in T cell-mediated antitumor immunity.
DNAX 辅助分子 1（DNAM-1）表达于所有 CD8(+) T 细胞上，可促进其活化和效应功能。DNAM-1 与 LFA-1 相互作用，LFA-1 是 T 细胞与 APC 之间形成免疫突触以及杀伤靶细胞所必需的关键分子。缺乏 DNAM-1 的小鼠表现出异常的 T 细胞反应和抗肿瘤活性，但具体机制尚不清楚。在本文中，我们发现，DNAM-1 缺陷导致 Ag 呈递后 CD8(+) T 细胞增殖减少和细胞毒性活性受损。我们还证明，DNAM-1 缺陷型 T 细胞与肿瘤细胞的结合减少，LFA-1 和脂筏向免疫突触的募集减少，这与体外肿瘤细胞杀伤减少相关。这种突触缺陷可能解释了为什么 DNAM-1 缺陷型小鼠不能在体内清除肿瘤，并强调了 DNAM-1 和免疫突触在 T 细胞介导的抗肿瘤免疫中的重要性。
