Franco M D, Nunes J, Lipcey C, Lopez M, Mawas C, Olive D
Unité 119 de l'Institut National de la Santé et de la Recherche Medicale, Marseille, France.
Cell Immunol. 1993 Nov;152(1):162-75. doi: 10.1006/cimm.1993.1276.
The human CD8 glycoprotein regulates the function of cytotoxic T cells activated by antigenic peptide as well as via CD3 or CD2 mAbs. Activation of T cells by CD2 mAbs requires two mAbs directed against distinct CD2 epitopes and induces tyrosine phosphorylation, PI-PLC activity generating the second messengers, IP3 and DAG, and finally lymphokine secretion. We have investigated the role of the CD8 alpha molecule in CD2-mediated activation of human cytotoxic T cell clones and CD8+ resting T cells. CD8 alpha-specific mAb inhibited 60% of the allospecific cytotoxicity of the CD8+ clone against its target cell and 86% of the CD2-redirected killing against the HLA Class I-negative Daudi target cell. In addition, CD8 alpha-specific mAb inhibited CD2-mediated TNF alpha and IL2 secretion by the CD8+ clone. Furthermore, CD8 alpha-specific mAb inhibited the increase in intracellular ionized calcium mediated by CD2 mAbs in the CD8+ clone and in purified T cells. Since the [Ca2+]i recruitment from internal stores induced by CD2 mAbs was inhibited, the inhibitory effect induced by the CD8 alpha-specific mAb probably acts on the PI-PLC activation pathway. This inhibition mechanism involves neither a decrease in affinity of CD2 mAb for its target nor a decrease in CD2 cell surface expression or a rise in cAMP known as an inhibitor of the CD2-mediated PI-PLC activity. These results suggest that the inhibitory mechanism induced by the CD8 mAb may prevent the activation of the PI-PLC activity, probably through the CD8 alpha-associated protein tyrosine kinase p56lck.
人类CD8糖蛋白可调节由抗原肽激活的细胞毒性T细胞的功能，以及通过CD3或CD2单克隆抗体激活的细胞毒性T细胞的功能。用CD2单克隆抗体激活T细胞需要两种针对不同CD2表位的单克隆抗体，并诱导酪氨酸磷酸化、磷脂酰肌醇特异性磷脂酶C（PI-PLC）活性，产生第二信使肌醇三磷酸（IP3）和二酰基甘油（DAG），最终分泌淋巴因子。我们研究了CD8α分子在CD2介导的人类细胞毒性T细胞克隆和CD8⁺静息T细胞激活中的作用。CD8α特异性单克隆抗体抑制了CD8⁺克隆对其靶细胞的同种特异性细胞毒性的60%，以及对HLA I类阴性Daudi靶细胞的CD2重定向杀伤的86%。此外，CD8α特异性单克隆抗体抑制了CD8⁺克隆由CD2介导的肿瘤坏死因子α（TNFα）和白细胞介素2（IL2）的分泌。此外，CD8α特异性单克隆抗体抑制了CD2单克隆抗体在CD8⁺克隆和纯化T细胞中介导的细胞内游离钙的增加。由于CD2单克隆抗体诱导的细胞内钙库钙离子募集受到抑制，CD8α特异性单克隆抗体诱导的抑制作用可能作用于PI-PLC激活途径。这种抑制机制既不涉及CD2单克隆抗体与其靶标的亲和力降低，也不涉及CD2细胞表面表达的降低或作为CD2介导的PI-PLC活性抑制剂的环磷酸腺苷（cAMP）的升高。这些结果表明，CD8单克隆抗体诱导的抑制机制可能通过与CD8α相关的蛋白酪氨酸激酶p56lck阻止PI-PLC活性的激活。
