Sancho D, Yáñez-Mó M, Tejedor R, Sánchez-Madrid F
Servicio de Inmulogía, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
Blood. 1999 Feb 1;93(3):886-96.
Cell adhesion molecules have a key role in the migration of T cells to inflammatory foci. However, the effect of the endothelial-lymphocyte interaction on the activation of the latter cells remains unresolved. We have studied the effect of resting and stimulated endothelial cells (ECs) on the activation of peripheral blood T cells (PBTLs), as assessed by the expression of CD69 and CD25 activation antigens. The incubation of PBTLs with tumor necrosis factor-alpha-activated EC monolayers, either alive or fixed, induced the expression of CD69 but not CD25, preferentially in the CD8(+) CD45RO+ cell subset. Furthermore, it induced the production of cytokines such as IFN-gamma, but not that of interleukin-2 (IL-2) and IL-4. EC treated with other stimuli such as IL-1beta, IFN-gamma, or lipopolysaccharide also showed the same proactivatory effect on T cells. Lymphocyte activation was almost completely inhibited by blocking anti-CD18 and anti-intercellular adhesion molecule-1 (anti-ICAM-1) monoclonal antibodies (MoAbs), but only slightly affected by MoAbs against CD49d, vascular cell adhesion molecule-1, and anti-IL-15. In addition, the interaction of PBTL with immobilized ICAM-1 induced CD69 expression in the same memory T-cell subset. IL-15 induced T-cell activation with expression of CD69 and CD25, and production of IFN-gamma, and its effect was additive with that triggered by cell adhesion to either EC or immobilized ICAM-1. The transmigration of PBTLs through either confluent EC monolayers or ICAM-1-coated membranes also induced efficiently the expression of CD69. When IL-15 was used as chemoattractant in these assays, a further enhancement in CD69 expression was observed in migrated cells. Together these results indicate that stimulated endothelium may have an important role in T-cell activation, through the lymphocyte function antigen-1/ICAM-1 pathway, and that IL-15 efficiently cooperates in this phenomenon. These observations could account for the abundance of CD69(+) cells in the lymphocytic infiltrates of several chronic inflammatory diseases.
细胞黏附分子在T细胞向炎症灶迁移中起关键作用。然而，内皮细胞与淋巴细胞的相互作用对后者细胞激活的影响仍未明确。我们研究了静息和刺激后的内皮细胞（ECs）对外周血T细胞（PBTLs）激活的影响，通过CD69和CD25激活抗原的表达来评估。将PBTLs与肿瘤坏死因子-α激活的EC单层细胞（活的或固定的）共孵育，可诱导CD69表达，但不诱导CD25表达，且优先在CD8(+) CD45RO+细胞亚群中诱导。此外，它还诱导细胞因子如IFN-γ的产生，但不诱导白细胞介素-2（IL-2）和IL-4的产生。用其他刺激物如IL-1β、IFN-γ或脂多糖处理的EC对T细胞也显示出相同的促激活作用。淋巴细胞激活几乎完全被阻断性抗CD18和抗细胞间黏附分子-1（抗ICAM-1）单克隆抗体（MoAbs）抑制，但仅受到抗CD49d、血管细胞黏附分子-1和抗IL-15的MoAbs轻微影响。此外，PBTL与固定化ICAM-1的相互作用在相同的记忆T细胞亚群中诱导CD69表达。IL-15通过诱导CD69和CD25表达以及IFN-γ产生来激活T细胞，其作用与细胞黏附于EC或固定化ICAM-1所触发的作用具有相加性。PBTLs通过汇合的EC单层细胞或ICAM-1包被的膜进行跨膜迁移也能有效诱导CD69表达。当在这些实验中使用IL-15作为趋化因子时，在迁移细胞中观察到CD69表达进一步增强。这些结果共同表明，刺激后的内皮细胞可能通过淋巴细胞功能抗原-1/ICAM-1途径在T细胞激活中起重要作用，并且IL-15在这一现象中有效协同作用。这些观察结果可以解释几种慢性炎症疾病淋巴细胞浸润中CD69(+)细胞的丰富现象。
