Fan S T, Brian A A, Lollo B A, Mackman N, Shen N L, Edgington T S
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Cell Immunol. 1993 Apr 15;148(1):48-59. doi: 10.1006/cimm.1993.1090.
To study the signaling role of CD11a/CD18 in the early events of T cell activation we have examined the induction of transcription of two important cytokines, namely TNF alpha and IL-2. Human peripheral blood T cells were stimulated with PMA/ionophore or immobilized anti-CD3 mAb (OKT3) with or without CD11a/CD18 engagement. Induced cytokine production by immobilized OKT3 was enhanced (3- to 10-fold) in cells adhering to OKT3 and ICAM-1 coimmobilized surfaces and anti-CD11a mAb abolished this enhancement effect. Similarly, inhibition of the PMA/ionophore-induced CD11a/CD18-mediated homotypic aggregations of T cells by mAbs specific for either CD11a or ICAM-1 reduced the induced cytokine production by more than 70%. We have also observed that greatly enhanced cytokine production resulted from cellular interactions between activated T cells and monolayers of endothelial cells. This enhancement was inhibited by a combination of CD11a-, CD18-, and ICAM-1-specific mAbs implicating a role of CD11a/CD18 in leukocyte adhesion to endothelium and diapedesis as part of the inflammatory process. By Northern analyses induced TNF alpha mRNA expression was significantly enhanced by the engagement of CD11a/CD18 in all the conditions mentioned above. These results, together with our previous studies on monocytes, lead to the conclusion that engagement of the CD11/CD18 family of receptors results in the transduction of cellular signals that quantitatively enhance the expression of important leukocyte-mediated immune and inflammatory responses.
为研究CD11a/CD18在T细胞激活早期事件中的信号传导作用，我们检测了两种重要细胞因子，即肿瘤坏死因子α（TNFα）和白细胞介素-2（IL-2）转录的诱导情况。用人外周血T细胞分别用佛波酯/离子载体或固定化抗CD3单克隆抗体（OKT3）刺激，同时有或没有CD11a/CD18参与。在黏附于OKT3和细胞间黏附分子-1（ICAM-1）共固定化表面的细胞中，固定化OKT3诱导的细胞因子产生增强（3至10倍），而抗CD11a单克隆抗体消除了这种增强作用。同样，用针对CD11a或ICAM-1的单克隆抗体抑制佛波酯/离子载体诱导的T细胞CD11a/CD18介导的同型聚集，可使诱导的细胞因子产生减少70%以上。我们还观察到，活化T细胞与内皮细胞单层之间的细胞相互作用导致细胞因子产生大幅增强。这种增强被CD11a、CD18和ICAM-1特异性单克隆抗体的组合所抑制，这表明CD11a/CD18在白细胞黏附于内皮和渗出过程中起作用，这是炎症过程的一部分。通过Northern分析，在上述所有条件下，CD11a/CD18的参与均显著增强了诱导的TNFα mRNA表达。这些结果，连同我们先前对单核细胞的研究，得出结论：CD11/CD18受体家族的参与导致细胞信号转导，从而定量增强重要的白细胞介导的免疫和炎症反应的表达。
