Pawelec G, Friccius H, Boshell M, Siegels-Hübenthal P, Rehbein A, Schlotz E, Pohla H, Schaudt K, Sansom D
Second Department of Internal Medicine, University Hospital, Tübingen, Federal Republic of Germany.
Cell Immunol. 1995 Apr 15;162(1):8-15. doi: 10.1006/cimm.1995.1045.
A condition of hyporesponsiveness can be induced in certain mature human alpha beta (TCR2) cells relatively easily by their stimulation in the absence of costimulatory signals (signal 1 alone). This state of "anergy" has been implicated in tolerance to self and transplanted organs as well as tumors and may represent an important regulatory component of immune responsiveness. Little is known about whether the same condition applies to gamma delta (TCR1) cells. We therefore undertook to investigate anergy induction in TCR1 cell clones using several approaches known to induce this state in TCR2 cells. First, TCR1 clones were found not to be anergized by culture on immobilized CD3 monoclonal antibody (mAb), while the majority of TCR2 clones were anergized. Second, blocking of autocrine proliferation (stimulated in TCR1 or TCR2 clones by mitogen in the presence of accessory cells) using CTLA-4-lg, a soluble B7 family counterreceptor resulted in anergy induction in TCR2 cells but not TCR1 cells, although experiments with CHO cells transfected with B7-1 (CD80) genes confirmed that these TCR1 clones were responsive to costimulation with B7. Third, blocking mitogen-induced proliferation with anti-IL 2 receptor antibodies and anti-IL 2 antisera resulted in anergy induction in TCR2 but not TCR1 cells. Fourth, stimulation with the calcium ionophore ionomycin also anergized TCR2 but not TCR1 cells. In all four systems, but especially in the latter, stimulation by signal 1 alone resulted in high levels of cell death (> 50%) which was similar for both TCR1 and TCR2 cells. Therefore, these data may reflect a high level of resistance to tolerance induction (manifested as proliferative anergy) but not to clonal deletion (manifested as stimulation-dependent cell death) on the part of TCR1 cells.
在缺乏共刺激信号（仅信号1）的情况下刺激某些成熟的人αβ（TCR2）细胞，相对容易诱导出低反应性状态。这种“无反应性”状态与对自身、移植器官以及肿瘤的耐受性有关，可能代表免疫反应性的一个重要调节成分。对于γδ（TCR1）细胞是否也存在同样的情况，人们了解甚少。因此，我们采用几种已知能在TCR2细胞中诱导这种状态的方法，来研究TCR1细胞克隆中的无反应性诱导。首先，发现TCR1克隆在固定化CD3单克隆抗体（mAb）上培养时不会出现无反应性，而大多数TCR2克隆会出现无反应性。其次，使用可溶性B7家族共受体CTLA-4-lg阻断自分泌增殖（在有辅助细胞存在的情况下，由丝裂原在TCR1或TCR2克隆中刺激），可在TCR2细胞中诱导出无反应性，但在TCR1细胞中则不会，尽管用转染了B7-1（CD80）基因的CHO细胞进行的实验证实，这些TCR1克隆对B7共刺激有反应。第三，用抗IL-2受体抗体和抗IL-2抗血清阻断丝裂原诱导的增殖，可在TCR2细胞中诱导出无反应性，但在TCR1细胞中则不会。第四，用钙离子载体离子霉素刺激也可使TCR2细胞出现无反应性，但TCR1细胞则不会。在所有这四个系统中，尤其是在后者中，仅信号1刺激会导致高水平的细胞死亡（>50%），这在TCR1和TCR2细胞中是相似的。因此，这些数据可能反映出TCR1细胞对耐受性诱导（表现为增殖性无反应性）具有高度抗性，但对克隆清除（表现为刺激依赖性细胞死亡）并非如此。
