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ICAMs 对于初始 CD4+T 细胞与淋巴结 DC 之间功能性免疫突触并非必需。

ICAMs Are Not Obligatory for Functional Immune Synapses between Naive CD4 T Cells and Lymph Node DCs.

机构信息

Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.

Bioinformatics Unit, Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 76100, Israel.

出版信息

Cell Rep. 2018 Jan 23;22(4):849-859. doi: 10.1016/j.celrep.2017.12.103. Epub 2018 Jan 28.

Abstract

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.

摘要

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。

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