Institute of Immunology, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
Department of Hematology, West German Cancer Center (WTZ), University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
Nat Commun. 2018 Jul 2;9(1):2561. doi: 10.1038/s41467-018-04832-2.
Dysfunction of CD8 T cells can lead to the development of chronic viral infection. Identifying mechanisms responsible for such T cell dysfunction is therefore of great importance to understand how to prevent persistent viral infection. Here we show using lymphocytic choriomeningitis virus (LCMV) infection that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is fundamental for recruiting lymphocyte-specific protein kinase (Lck) into the T cell receptor complex to form an efficient immunological synapse. CEACAM1 is essential for activation of CD8 T cells, and the absence of CEACAM1 on virus-specific CD8 T cells limits the antiviral CD8 T cell response. Treatment with anti-CEACAM1 antibody stabilizes Lck in the immunological synapse, prevents CD8 T cell exhaustion, and improves control of virus infection in vivo. Treatment of human virus-specific CD8 T cells with anti-CEACAM1 antibody similarly enhances their proliferation. We conclude that CEACAM1 is an important regulator of virus-specific CD8 T cell functions in mice and humans and represents a promising therapeutic target for modulating CD8 T cells.
CD8 T 细胞功能障碍可导致慢性病毒感染的发生。因此，鉴定导致 T 细胞功能障碍的机制对于了解如何预防持续性病毒感染至关重要。在这里，我们利用淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染表明，癌胚抗原相关细胞黏附分子 1（CEACAM1）对于募集淋巴细胞特异性蛋白激酶（Lck）进入 T 细胞受体复合物形成有效的免疫突触是必不可少的。CEACAM1 对于 CD8 T 细胞的激活是必需的，病毒特异性 CD8 T 细胞上 CEACAM1 的缺失限制了抗病毒 CD8 T 细胞反应。用抗 CEACAM1 抗体治疗可稳定免疫突触中的 Lck，防止 CD8 T 细胞耗竭，并改善体内病毒感染的控制。用抗 CEACAM1 抗体处理人类病毒特异性 CD8 T 细胞同样增强了它们的增殖。我们得出结论，CEACAM1 是小鼠和人类病毒特异性 CD8 T 细胞功能的重要调节剂，代表了调节 CD8 T 细胞的有前途的治疗靶标。
