Ciubotariu R, Colovai A I, Pennesi G, Liu Z, Smith D, Berlocco P, Cortesini R, Suciu-Foca N
College of Physicians and Surgeons of Columbia University, Department of Pathology, New York 10032, USA.
J Immunol. 1998 Nov 15;161(10):5193-202.
Evidence that T cells can down-regulate the immune response by producing or consuming certain cytokines or by lysing APCs or Th cells has been provided in various systems. However, the generation and characterization of suppressor T cell lines have met with limited success. Here we show that xenospecific suppressor T cells can be generated by in vitro stimulation of human T cells with pig APCs. Similar to allospecific suppressors, these xenospecific suppressor T cells carry the CD8+CD28- phenotype and react to MHC class I Ags expressed by the APCs used for priming. TCR spectratyping of T suppressor cells showed oligoclonal usage of TCR-Vbeta families, indicating that xenostimulation of CD8+CD28- T cells results in Ag-driven selection of a limited Vbeta repertoire. Xenospecific T suppressor cells prevent the up-regulation of CD154 molecules on the membrane of Th cells, inhibiting their ability to react against the immunizing MHC class II xenoantigens. The mechanism of this suppression, therefore, appears to be blockade of CD154/CD40 interaction required for efficient costimulation of activated T cells.
在多种系统中都已证实，T细胞可通过产生或消耗某些细胞因子、裂解抗原呈递细胞（APC）或辅助性T细胞（Th细胞）来下调免疫反应。然而，抑制性T细胞系的生成及特性鉴定仅取得了有限的成功。在此我们表明，通过用猪APC体外刺激人T细胞可生成异种特异性抑制性T细胞。与同种特异性抑制细胞相似，这些异种特异性抑制性T细胞具有CD8⁺CD28⁻表型，并对用于启动的APC所表达的MHC I类抗原产生反应。对抑制性T细胞进行TCR谱型分析显示，TCR-Vβ家族存在寡克隆使用情况，这表明对CD8⁺CD28⁻T细胞进行异种刺激会导致有限的Vβ库在抗原驱动下被选择。异种特异性T抑制细胞可阻止Th细胞膜上CD154分子的上调，抑制其对免疫性MHC II类异种抗原作出反应的能力。因此，这种抑制机制似乎是阻断了活化T细胞有效共刺激所需的CD154/CD40相互作用。
