Gerli R, Agea E, Muscat C, Tognellini R, Fiorucci G, Spinozzi F, Cernetti C, Bertotto A
Policlinico di Monteluce, University of Perugia, Italy.
Cell Immunol. 1993 Apr 15;148(1):32-47. doi: 10.1006/cimm.1993.1089.
As cord T cells, a model of antigen (Ag)-unprimed cell, display a functional defect when stimulated through the CD3 molecule, the role of lymphocyte function-associated antigen 1(LFA-1)/intercellular adhesion molecule 1 (ICAM-1) and CD2/lymphocyte function-associated antigen 3 (LFA-3) receptor-ligand pairs in cord CD3-triggered T-cell activation was analyzed using specific monoclonal antibodies (mAb) against each adhesion molecule. The addition of anti-CD11a, anti-CD18, or anti-CD2 to both adult and cord peripheral blood mononuclear cells (PBMC) cultures led to a decrease in CD3-induced proliferation. In contrast, CD3-stimulated cord, but not adult, PBMC proliferation was markedly enhanced when anti-CD54 or anti-CD58 were added. Despite the fact that ICAM-1 and LFA-3 molecules were virtually absent on cord resting T cells, mAb against these two molecules boosted both mitogenesis of and interleukin (IL)-2 production by purified cord T cells stimulated with plastic immobilized anti-CD3. Cord T-cell supernatant levels of interferon-gamma (IFN-gamma) were undetectable with CD3 stimulation, slightly raised with CD58/CD3 costimulation, but normal when T cells were preincubated with IL-2 for 24 hr before being costimulated with anti-CD3/CD58. Evidence that IL-2 and IFN-gamma play a pivotal role in fully activating cord T cells came from the demonstration that IL-2 and IFN-gamma are able to bypass the CD3-proliferative defect through differential up-regulation of the adhesion molecules. It would, therefore, seem that ICAM-1 and LFA-3 molecules are crucially implicated in the CD3-activation pathway of Ag-unprimed T cells.
作为未接触抗原（Ag）细胞的模型，脐带血T细胞在通过CD3分子刺激时表现出功能缺陷。本研究使用针对各黏附分子的特异性单克隆抗体（mAb），分析淋巴细胞功能相关抗原1（LFA-1）/细胞间黏附分子1（ICAM-1）和CD2/淋巴细胞功能相关抗原3（LFA-3）受体-配体对在脐带血CD3触发的T细胞活化中的作用。向成人和脐带血外周血单个核细胞（PBMC）培养物中添加抗CD11a、抗CD18或抗CD2，导致CD3诱导的增殖减少。相反，添加抗CD54或抗CD58时，CD3刺激的脐带血PBMC增殖显著增强，而成人PBMC增殖无明显变化。尽管在脐带血静止T细胞上几乎不存在ICAM-1和LFA-3分子，但针对这两种分子的mAb增强了塑料固定抗CD3刺激的纯化脐带血T细胞的有丝分裂和白细胞介素（IL）-2的产生。CD3刺激时，脐带血T细胞上清液中干扰素-γ（IFN-γ）水平无法检测到，CD58/CD3共刺激时略有升高，但在用抗CD3/CD58共刺激前用IL-2预孵育24小时的T细胞中，IFN-γ水平正常。IL-2和IFN-γ在完全激活脐带血T细胞中起关键作用的证据来自于以下证明：IL-2和IFN-γ能够通过黏附分子的差异上调绕过CD3增殖缺陷。因此，ICAM-1和LFA-3分子似乎在未接触Ag的T细胞的CD3激活途径中起关键作用。
