Damle N K, Doyle L V
Department of Immunology, CETUS Corporation, Emeryville, CA 94608.
J Immunol. 1990 Feb 15;144(4):1233-40.
The accumulation of mononuclear cells at sites of chronic inflammation is dependent on a number of factors including localized adherence of lymphocytes to vascular endothelial cells (EC), cytokine-mediated increased adhesiveness of endothelium, chemotactic factors and endothelial permeability. The present study investigates two of the above attributes of lymphocyte-EC interaction: namely, the ability of maturationally distinct subpopulations of human T lymphocytes to adhere to vascular EC and to increase vascular endothelial permeability to macromolecules in an in vitro model. Thus, human T lymphocytes were separated into CD4+ CD8-helper/inducer, CD4- CD8+ cytotoxic/suppressor, CD29+ CD45RA- CD45RO+ memory, and CD29- CD45RA+ CD45RO- naive/virgin T subpopulations, were activated with PHA and PMA, and then examined for their adherence to EC and also for their effect on endothelial permeability. Upon activation, cells within each of the above four subpopulations exhibited increased adherence to EC. In contrast, resting CD29+ CD45RA- CD45RO+ memory T lymphocytes exhibited two to three times greater ability to adhere to EC than their CD29- CD45RA+ CD45RO- naive/virgin counterparts. Consistent with their increased adherence to EC, CD29+ CD45RO+ memory T lymphocytes, when activated, significantly increased endothelial permeability to albumin. Although activated CD45RA+ naive T lymphocytes exhibited increased adherence to EC, these cells failed to increase significantly endothelial permeability. Similar to their polyclonal counterparts, Ag-specific CD4+ CD29+ CD45RO+ T cell clones, but not their actively released mediators, also increased endothelial permeability via a noncytolytic mechanism(s). This ability of CD29+ CD45RO+ memory T lymphocytes to augment endothelial permeability may facilitate their transendothelial migration into extravascular space. These observations may provide additional insights into molecular mechanism(s) underlying pathophysiology of localized chronic inflammatory responses in general and more specifically selective accumulation of CD29+/CD45RO+ memory T lymphocytes at sites of chronic inflammation such as rheumatoid synovium.
慢性炎症部位单核细胞的积聚取决于多种因素，包括淋巴细胞与血管内皮细胞（EC）的局部黏附、细胞因子介导的内皮细胞黏附性增加、趋化因子以及内皮通透性。本研究调查了淋巴细胞与内皮细胞相互作用的上述两个特性：即在体外模型中，成熟程度不同的人T淋巴细胞亚群黏附于血管内皮细胞以及增加血管内皮对大分子通透性的能力。因此，将人T淋巴细胞分离为CD4 + CD8 -辅助/诱导型、CD4 - CD8 +细胞毒性/抑制型、CD29 + CD45RA - CD45RO +记忆型和CD29 - CD45RA + CD45RO -初始/未致敏T亚群，用PHA和PMA激活，然后检测它们对内皮细胞的黏附以及对内皮通透性的影响。激活后，上述四个亚群中的每个亚群的细胞对内皮细胞的黏附均增加。相比之下，静息的CD29 + CD45RA - CD45RO +记忆T淋巴细胞黏附于内皮细胞的能力比其CD29 - CD45RA + CD45RO -初始/未致敏对应细胞高两到三倍。与它们对内皮细胞黏附增加一致，CD29 + CD45RO +记忆T淋巴细胞激活后，显著增加了内皮对白蛋白的通透性。虽然激活的CD45RA +初始T淋巴细胞对内皮细胞的黏附增加，但这些细胞未能显著增加内皮通透性。与多克隆对应细胞相似，抗原特异性CD4 + CD29 + CD45RO + T细胞克隆，而非其主动释放的介质，也通过非细胞溶解机制增加内皮通透性。CD29 + CD45RO +记忆T淋巴细胞增强内皮通透性的这种能力可能促进它们经内皮迁移到血管外间隙。这些观察结果可能为一般局部慢性炎症反应的病理生理学，更具体地为类风湿滑膜等慢性炎症部位CD29 + /CD45RO +记忆T淋巴细胞的选择性积聚的潜在分子机制提供更多见解。
