Bertotto A, Gerli R, Lanfrancone L, Crupi S, Arcangeli C, Cernetti C, Spinozzi F, Rambotti P
Department of Pediatrics, University of Perugia, Italy.
Cell Immunol. 1990 May;127(2):247-59. doi: 10.1016/0008-8749(90)90130-j.
Despite the fact that the percentage of circulating CD3-positive cells is similar in cord and adult blood, the proliferative response induced by anti-CD3 monoclonal antibody (mAb) was impaired in the majority of human cord peripheral blood mononuclear cell (PBMC) samples we tested. The cell proliferative defect was associated with low interleukin 2 (IL 2) gene expression and scant IL 2 production. However, interleukin 2 receptor was fully expressed at both the mRNA and protein levels. Such a finding is consistent with the observation that exogenous recombinant IL 2 is able to boost the anti-CD3-mediated response of cord PBMC. Furthermore, when anti-CD3 and phorbol myristate acetate (PMA) were added together, they exerted a very marked synergistic effect on both the proliferation of, and IL 2 production by, cord PBMC. The addition of allogeneic antigen presenting cells plus soluble anti-CD3 or Sepharose-coupled anti-CD3 mAb to the cord T cell cultures had no significant effect on proliferation, whereas both elicited good mitogenesis of adult T cells. Moreover, addition of exogenous recombinant interleukin 1 to anti-CD3-stimulated T cells failed to trigger any proliferation in either adult or cord samples. Since the combination of PMA and calcium ionophore A23187 is effective in triggering optimal proliferation of cord T cells, the defect would seem to be associated with a failure in transmembrane transduction of the activation signals provided by the anti-CD3 stimulus for the cord T cell.
尽管循环中CD3阳性细胞在脐带血和成人血液中的百分比相似，但在我们检测的大多数人脐带外周血单个核细胞（PBMC）样本中，抗CD3单克隆抗体（mAb）诱导的增殖反应受损。细胞增殖缺陷与白细胞介素2（IL-2）基因表达水平低和IL-2产生量少有关。然而，白细胞介素2受体在mRNA和蛋白质水平均充分表达。这一发现与外源性重组IL-2能够增强脐带血PBMC的抗CD3介导反应的观察结果一致。此外，当抗CD3和佛波酯肉豆蔻酸酯（PMA）一起添加时，它们对脐带血PBMC的增殖和IL-2产生均发挥了非常显著的协同作用。向脐带血T细胞培养物中添加同种异体抗原呈递细胞加可溶性抗CD3或琼脂糖偶联抗CD3 mAb对增殖没有显著影响，而两者均能引起成人T细胞良好的有丝分裂。此外，向抗CD3刺激的T细胞中添加外源性重组白细胞介素1未能在成人或脐带血样本中引发任何增殖。由于PMA和钙离子载体A23187的组合可有效触发脐带血T细胞的最佳增殖，因此该缺陷似乎与抗CD3刺激为脐带血T细胞提供的激活信号跨膜转导失败有关。
