Kaiser M, Brooks-Kaiser J, Fitzpatrick L, Bleackley R C, Hoskin D W
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
J Leukoc Biol. 1993 Nov;54(5):458-64. doi: 10.1002/jlb.54.5.458.
We have examined the role of interleukin (IL) 2 in the expression of cytotoxic cell proteinases (CCP) 1 and 2, as well as in the induction of major histocompatibility complex (MHC)-unrestricted cytotoxic activity in murine T cell cultures following stimulation with anti-CD3 monoclonal antibody. A dramatic reduction in CCP-1 and CCP-2 gene expression and near absence of cytolytic activity was shown to occur in these cultures when the expression of IL-2 was inhibited by 10(-6) M cyclosporin A (CsA). The inhibitory effect of CsA could not be eliminated by the addition to culture of recombinant IL-2 at concentrations typically present in anti-CD3-stimulated T cell culture supernatants. Furthermore, when endogenous IL-2 (45-60 U/ml) present in anti-CD3-stimulated T cell cultures was neutralized with anti-mouse IL-2 antibody there was no effect on CCP-1 and CCP-2 mRNA expression and only a slight decrease in cytolytic activity. The expression of CCP-1 and CCP-2 gene products and the induction of MHC-unrestricted cytotoxic activity in anti-CD3-stimulated T cell cultures therefore occur independently of IL-2 synthesis but are regulated by a CsA-sensitive mechanism.
我们研究了白细胞介素（IL）-2在细胞毒性细胞蛋白酶（CCP）-1和CCP-2表达中的作用，以及在抗CD3单克隆抗体刺激后的小鼠T细胞培养物中诱导主要组织相容性复合体（MHC）非限制性细胞毒性活性的作用。当用10^(-6) M环孢素A（CsA）抑制IL-2的表达时，这些培养物中显示出CCP-1和CCP-2基因表达显著降低且几乎没有细胞溶解活性。在培养物中添加通常存在于抗CD3刺激的T细胞培养上清液中的重组IL-2浓度，无法消除CsA的抑制作用。此外，当用抗小鼠IL-2抗体中和抗CD3刺激的T细胞培养物中存在的内源性IL-2（45 - 60 U/ml）时，对CCP-1和CCP-2 mRNA表达没有影响，细胞溶解活性仅略有下降。因此，在抗CD3刺激的T细胞培养物中，CCP-1和CCP-2基因产物的表达以及MHC非限制性细胞毒性活性的诱导独立于IL-2合成，但受CsA敏感机制调节。
