Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Bioinformatics Unit, Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 76100, Israel.
Cell Rep. 2018 Jan 23;22(4):849-859. doi: 10.1016/j.celrep.2017.12.103. Epub 2018 Jan 28.
Protective immune responses depend on the formation of immune synapses between T cells and antigen-presenting cells (APCs). The two main LFA-1 ligands, ICAM-1 and ICAM-2, are co-expressed on many cell types, including APCs and blood vessels. Although these molecules were suggested to be key players in immune synapses studied in vitro, their contribution to helper T cell priming in vivo is unclear. Here, we used transgenic mice and intravital imaging to examine the role of dendritic cell (DC) ICAM-1 and ICAM-2 in naive CD4 T cell priming and differentiation in skin-draining lymph nodes. Surprisingly, ICAM deficiency on endogenous CD40-stimulated lymph node DCs did not impair their ability to arrest and prime CD4 lymphocyte activation and differentiation into Th1 and Tfh effectors. Thus, functional T cell receptor (TCR)-specific helper T cell synapses with antigen-presenting DCs and subsequent proliferation and early differentiation into T effectors do not require LFA-1-mediated T cell adhesiveness to DC ICAMs.
保护性免疫反应依赖于 T 细胞和抗原呈递细胞 (APCs) 之间免疫突触的形成。两种主要的 LFA-1 配体,ICAM-1 和 ICAM-2,在许多细胞类型上共表达,包括 APC 和血管。尽管这些分子被认为是体外研究免疫突触的关键因素,但它们对辅助 T 细胞在体内的启动作用尚不清楚。在这里,我们使用转基因小鼠和活体成像技术研究了树突状细胞 (DC) ICAM-1 和 ICAM-2 在皮肤引流淋巴结中初始 CD4 T 细胞启动和分化中的作用。令人惊讶的是,内源性 CD40 刺激的淋巴结 DC 上的 ICAM 缺乏并不损害它们捕获和启动 CD4 淋巴细胞激活以及分化为 Th1 和 Tfh 效应物的能力。因此,具有功能性 T 细胞受体 (TCR) 的辅助 T 细胞与抗原呈递 DC 的突触以及随后的增殖和早期分化为 T 效应物不需要 LFA-1 介导的 T 细胞对 DC ICAMs 的黏附性。