Lymphocyte Interactions with Endothelial Cells-猫眼课题宝

淋巴细胞与内皮细胞的相互作用

DOI：

10.1007/978-1-4684-5296-9_25

发表时间：

1987

期刊：

Journal of interferon research

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

J. Pober

血管系统的内皮衬里形成血管壁和外周组织与血液的界面。因此，循环淋巴细胞必须接触内皮细胞，因为它们回到免疫炎症部位。从形态学上看，淋巴细胞和内皮细胞在这一过程中都出现了“激活”，但激活过程的细节和机制还没有完全了解。我们使用培养的人内皮细胞（HEC）和外周血单核细胞（PBMC）来研究这些细胞类型之间的潜在相互作用。在大量共培养中，HEC激活同种异体T细胞，导致PBMC增殖。相反，真皮成纤维细胞或血管平滑肌细胞不诱导同种异体PBMC增殖。HEC改变PBMC对外源性刺激的反应;在由植物血凝素刺激的PBMC培养物中包含HEC导致PBMC增殖增加和白细胞介素2产生的高达10倍或更大的增强。增殖的PBMC中的表型因HEC的存在而改变。在与PBMC共培养之前，HEC不表达主要组织相容性复合物（MHC）II类抗原，这是PBMC向同种异体PBMC增殖的主要刺激物。然而，在共培养的1-2天内，HEC均匀地表达II类分子。由于PBMC增殖在第4或5天开始，因此诱导的HEC II类分子可能参与T细胞活化。免疫干扰素（IFN-7），一种由活化的T细胞分泌的介质，通过诱导II类分子模拟共培养的效果。所有三个II类基因座（DR、DP、DQ）被激活，导致mRNA和表面抗原表达的从头出现。IFN-7还诱导真皮成纤维细胞或平滑肌细胞上的II类分子的定量相当的表达，但这样的细胞仍然不能刺激同种异体PBMC，即使在外源性白细胞介素1的存在下。这种“缺陷”似乎不太可能存在于II类分子的组织特异性结构差异中，因为IFN-γ处理的真皮成纤维细胞被II类特异性溶细胞性T淋巴细胞克隆裂解并激活克隆的辅助性T细胞。HEC与PBMC的共培养或用IFN-γ处理引起培养的HEC经历形态学变化。具体而言，IFN-γ处理的HEC变得丰满和伸长，重叠，重新排列其肌动蛋白丝，并失去其基质相关的纤连蛋白。这些形态学变化在IFN-γ处理的真皮成纤维细胞中未观察到，在HEC培养物中也不能由非免疫干扰素（IFN-α，s）诱导。肿瘤坏死因子（TNF）是活化的单核细胞的产物，在HEC培养物中引起IFN-γ样形态学变化。低浓度的TNF和IFN-γ协同作用，而高浓度的这些介质组合产生独特的效果。鼠单克隆抗体H4/18检测通过与PBMC共培养在HEC上诱导的抗原。与MHC抗原的调节相反，其在几天后达到平台并持续存在，H4/18识别的抗原在几小时内达到峰值并消失。这种瞬时诱导可以被TNF和白细胞介素1模拟，但不能被IFN-γ模拟。并与其他几种瞬时表达的HEC特性如促凝血活性和白细胞粘附性相似。这些研究表明，培养物中淋巴细胞和内皮细胞的相互作用改变了两种细胞的行为和表型，并提示淋巴因子单独或联合作用。可能会导致许多这种相互作用。

The endothelial lining of the vasculature forms the interface of the vessel wall and peripheral tissues with the blood. Therefore, circulating lymphocytes must contact endothelial cells as they home to a site of immune inflammation. Morphologically, both lymphocytes and endothelial cells appear “activated” during this encounter, but the details and mechanisms of the activation processes are not fully understood. We have used cultured human endothelial cells (HEC) and peripheral blood mononuclear cells (PBMC) to study potential interactions between these cell types. In bulk coculture, HEC activate allogeneic T cells, leading PBMC to proliferate. In contrast, dermal fibroblasts or vascular smooth muscle cells do not induce allogeneic PBMC proliferation. The HEC modify the response of PBMC to exogenous stimulation; inclusion of HEC in a culture of PBMC stimulated by phytohemagglutinin leads to increased PBMC proliferation and up to ten-fold or greater enhancement of interleukin 2 production. The phenotypes in the proliferating PBMC are altered by the presence of HEC. Prior to coculture with PBMC, HEC do not express class II major histocompatibility complex (MHC) antigens, the major stimulus of PBMC proliferation to allogeneic PBMC. However, within 1–2 days of coculture, the HEC uniformly express class II molecules. Since PBMC proliferation begins on day 4 or 5, the induced HEC class II molecules could be involved in the T cell activation. Immune interferon (IFN-7), a mediator secreted by activated T cells, mimics the effect of coculture by inducing class II molecules. All three class II loci (DR, DP, DQ) are activated, leading to de novo appearance of mRNA and surface antigen expression. The IFN-7 also induces quantitatively comparable expression of class II molecules on dermal fibroblasts or smooth muscle cells, but such cells still fail to stimulate allogeneic PBMC, even in the presence of exogenous interleukin 1. It appears unlikely that this “defect” resides in tissue-specific structural differences of the class II molecules, since IFN-γ-treated dermal fibroblasts are lysed by class-II-specific cytolytic T lymphocyte clones and activate cloned helper T cells. Coculture of HEC with PBMC or treatment with IFN-γ causes cultured HEC to undergo morphological changes. Specifically, IFN-γ-treated HEC become plump and elongated, overlap, rearrange their actin filaments, and lose their matrix-associated fibronectin. These morphological changes are not seen with IFN-γ-treated dermal fibroblasts, nor can they be induced in HEC cultures by nonimmune interferons (IFN-α,s). Tumor necrosis factor (TNF), a product of activated monocytes, causes IFN-γ-like morphological changes in HEC cultures. Low concentrations of TNF and IFN-γ act synergistically, whereas higher concentrations of these mediators in combination produce unique effects. Murine monoclonal antibody H4/18 detects an antigen induced on HEC by coculture with PBMC. In contrast to the modulation of MHC antigens, which plateau after several days and persist, the antigen recognized by H4/18 peaks in several hours and disappears. This transient induction can be mimicked by TNF and interleukin 1, but not IFN--y. and parallels several othcr transicntly expressed HEC properties such as procoagulant activity and leukocyte adhesion. These studies demonstrate that the interaction of lymphocytes and endothelium in culiure alters the behavior and phenotype of both cells and suggest that lymphokines, acting separatcly and in combination. may mediale many of these interactions.