Hambor J E, Kaplan D R, Tykocinski M L
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
J Immunol. 1990 Sep 15;145(6):1646-52.
Antisense and sense transfection technologies were employed in cellular coculture systems to investigate the physiologic requirements for CD8-dependent immunoregulation. Our data indicate that cells bearing genetically engineered CD8 molecules incorporating a glycoinositolphospholipid membrane anchor, as well as fixed cells bearing natural CD8 molecules, retain specific, CD8-dependent immunoregulatory activity. These findings together support the novel concept that CD8, a molecule traditionally thought of as a receptor, can function as an inhibitory ligand. CD8-dependent inhibition was shown to induce nonresponsiveness, persisting for at least 24 h, in Ag-specific responders. Moreover, only cells undergoing primary, but not secondary, antigenic stimulation through their TCR were found to be susceptible to CD8-dependent inhibition. Both CD4+ and CD8+ responding T cells were inhibited by CD8+ modulatory cells. These functional analyses of inhibitory and responder cells in CD8-dependent inhibition lay the groundwork for developing artificial CD8-based immunomodulatory peptides and deciphering CD8's role in natural immunoregulation.
在细胞共培养系统中采用反义及正义转染技术，以研究CD8依赖性免疫调节的生理需求。我们的数据表明，携带经基因工程改造的、含有糖基磷脂酰肌醇膜锚定物的CD8分子的细胞，以及携带天然CD8分子的固定细胞，均保留特异性的、CD8依赖性免疫调节活性。这些发现共同支持了一个新的概念，即传统上被认为是一种受体的CD8分子，可以作为一种抑制性配体发挥作用。已表明，在抗原特异性应答细胞中，CD8依赖性抑制可诱导无反应性，这种无反应性持续至少24小时。此外，发现只有通过其TCR经历初次而非二次抗原刺激的细胞才易受CD8依赖性抑制的影响。CD4+和CD8+应答性T细胞均受到CD8+调节细胞的抑制。对CD8依赖性抑制中的抑制细胞和应答细胞的这些功能分析，为开发基于人工CD8的免疫调节肽以及解读CD8在天然免疫调节中的作用奠定了基础。
