Stewart B H, Hoskin D W
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Immunol Invest. 1997 Aug-Dec;26(5-7):601-14. doi: 10.3109/08820139709088544.
Antigen-nonspecific CD8+ cytotoxic T cells induced with anti-CD3 monoclonal antibody (mAb) are able to kill tumor cells in a major histocompatibility complex (MHC)-unrestricted fashion. However, the role of CD8 in the MHC-independent tumoricidal activity of anti-CD3-activated killer T (AK-T) cells has not been investigated. Here we show that anti-CD8 alpha mAb inhibits, in a dose-dependent fashion, lysis of P815 and YAC-1 tumor cells by mouse AK-T cells. The inhibition of MHC-unrestricted cytotoxicity by anti-CD8 alpha mAb cannot be attributed to interference with an adhesion-like function of CD8 towards class I MHC molecules on the target cells because anti-CD8 alpha mAb (i) had equal inhibitory effects on the cytolysis of tumor target cells regardless of their relative level of class I MHC molecule expression and (ii) did not interfere with the formation of conjugates between AK-T cells and class I MHC-bearing P815 tumor cells. However, anti-CD8 alpha mAb abrogated AK-T cell granule exocytosis in the presence of P815 tumor cells, indicating a regulatory role for CD8 in the signal transduction events which result in lysis of the tumor target cells. Immunoblot analysis of the post-nuclear fraction of lysates from AK-T cells exposed to P815 tumor cells in the presence of anti-CD8 alpha mAb revealed reduced phosphorylation of tyrosine residues on a protein with an Mr of approximately 62 kDa. Taken together, these data suggest that CD8 is able to affect the tumoricidal activity of MHC-unrestricted AK-T cells independent of class I MHC molecules on the target cell.
用抗CD3单克隆抗体（mAb）诱导产生的抗原非特异性CD8 + 细胞毒性T细胞能够以主要组织相容性复合体（MHC）非限制性方式杀伤肿瘤细胞。然而，CD8在抗CD3激活的杀伤性T（AK-T）细胞的MHC非依赖性杀瘤活性中的作用尚未得到研究。在此我们表明，抗CD8α mAb以剂量依赖性方式抑制小鼠AK-T细胞对P815和YAC-1肿瘤细胞的裂解。抗CD8α mAb对MHC非限制性细胞毒性的抑制不能归因于其干扰CD8对靶细胞上I类MHC分子的黏附样功能，因为抗CD8α mAb：（i）对肿瘤靶细胞的细胞溶解具有同等抑制作用，而不论其I类MHC分子表达的相对水平如何；（ii）不干扰AK-T细胞与携带I类MHC的P815肿瘤细胞之间结合物的形成。然而，抗CD8α mAb在存在P815肿瘤细胞的情况下消除了AK-T细胞颗粒的胞吐作用，表明CD8在导致肿瘤靶细胞裂解的信号转导事件中起调节作用。对抗CD8α mAb存在下暴露于P815肿瘤细胞的AK-T细胞裂解物的核后组分进行免疫印迹分析，结果显示，一个分子量约为62 kDa的蛋白质上酪氨酸残基的磷酸化减少。综上所述，这些数据表明，CD8能够独立于靶细胞上的I类MHC分子影响MHC非限制性AK-T细胞的杀瘤活性。
