Department of Dermatology, University Hospital Heidelberg, Vossstrasse 11, 69115 Heidelberg, Germany.
J Allergy Clin Immunol. 2010 Jan;125(1):237-46.e1-7. doi: 10.1016/j.jaci.2009.10.025.
Regulatory T (Treg) cells suppress the sensitization phase of experimental contact hypersensitivity (CHS) reactions when injected before hapten application.
Our aim was to analyze the mechanisms by which Treg cells suppress the sensitization phase of CHS reactions.
Treg cells were labeled with different fluorescent dyes and injected into naive mice directly before sensitization with the hapten 2,4,6-trinitro-1-chlorobenzene. Two days after sensitization, the lymphoid organs were analyzed for the presence of Treg cells and engagement of gap junctions with other cells. Dendritic cells (DCs) and effector CD8(+)T cells were isolated from the draining lymph nodes (LNs) of the differently treated groups, analyzed by using FACS for activation markers, and assessed for the T-cell stimulatory capacity of the DCs and the priming of effector T cells.
Only the LN-homing Treg cells suppressed the sensitization phase in CHS reactions by means of establishing gap junctions with DCs in the dLNs. This gap junctional intercellular communication led to downregulation of T-cell costimulatory molecules on the surface of the DCs, abrogating the priming, activation, and proliferation of hapten-specific CD8(+)T cells. Consequently, the ear-swelling response induced by challenge with the respective hapten was prevented.
Treg cells not only modulate ongoing CD4(+)T cell-mediated immune reactions at tissue sites but also abrogate the de novo induction of CD8(+)T cell-driven immune reactions by interfering with T-cell stimulatory activity of DCs through gap junctional intercellular communication.
调节性 T（Treg）细胞在半抗原应用前注射时可抑制实验性接触超敏反应（CHS）反应的致敏阶段。
我们旨在分析 Treg 细胞抑制 CHS 反应致敏阶段的机制。
用不同荧光染料标记 Treg 细胞，在用半抗原 2,4,6-三硝基-1-氯苯致敏前直接注射入 naive 小鼠。致敏后 2 天，分析淋巴器官中 Treg 细胞的存在和与其他细胞的缝隙连接的形成。从用不同方法处理的组的引流淋巴结（LN）中分离出树突状细胞（DC）和效应 CD8+T 细胞，用 FACS 分析激活标志物，并评估 DC 的 T 细胞刺激能力和效应 T 细胞的启动。
只有 LN 归巢的 Treg 细胞通过与 dLN 中的 DC 建立缝隙连接，抑制 CHS 反应的致敏阶段。这种缝隙连接细胞间通讯导致 DC 表面 T 细胞共刺激分子的下调，从而阻断了半抗原特异性 CD8+T 细胞的启动、激活和增殖。因此，防止了用相应半抗原挑战引起的耳部肿胀反应。
Treg 细胞不仅在组织部位调节正在进行的 CD4+T 细胞介导的免疫反应，而且通过缝隙连接细胞间通讯干扰 DC 的 T 细胞刺激活性，从而阻止 CD8+T 细胞驱动的免疫反应的新诱导。
