Nisini R, Fattorossi A, Ferlini C, D'Amelio R
Divisione Aerea Studie Richerche e Sperimentazione, Lab. Immunologia, Pomezia, Roma, Italy.
Eur J Immunol. 1996 Apr;26(4):797-803. doi: 10.1002/eji.1830260411.
Human T cell clones (TCC) are antigen-presenting cells (APC) able to present peptides and superantigens (SAg) and to process and present intact proteins. TCC express major histocompatibility complex (MHC) class II antigens and molecules involved in the accessory signal delivery, such as B7.1 and B7.2/B70. Notwithstanding these observations, the role of professional APC has been often denied to T cells because anergy of responder T cells rather than proliferation has been observed following the TCC presentation in the absence of added professional APC. Here, we show that upon stimulation with free SAg, TCC undergo proliferative responses followed, after a 1-week culture, by an SAg-dependent unresponsiveness to T cell receptor (TCR)-mediated stimuli, but not to interleukin-2. The anergy induced by the SAg can not be prevented by the addition of autologous Epstein-Barr virus (EBV)-transformed B cells, indicating that the induction of anergy occurs also in the presence of conventional APC. Conversely, if the TCC are stimulated by SAg-prepulsed irradiated APC, either EBV and TCC, the induction of anergy is not observed. After a 1-week culture, in fact, TCC stimulated with APC-bound SAg responded to TCR-mediated stimuli, irrespective of the APC (EBV or TCC) used for the SAg presentation. Stimulation of TCC with free SAg in a semisolid medium that prevents T-T cell contacts resulted in an activation followed by a state of anergy, suggesting that anergy is the consequence of SAg recognition at the single T cell level. These data indicate that the anergy observed in TCC upon a 1-week culture in the presence of soluble SAg is not the result of an inherent inability of TCC to act as professional APC. Rather the phenomenon depends on the presence of soluble SAg, leading to T cell autostimulation.
人T细胞克隆（TCC）是能够呈递肽和超抗原（SAg）并加工呈递完整蛋白质的抗原呈递细胞（APC）。TCC表达主要组织相容性复合体（MHC）II类抗原以及参与辅助信号传递的分子，如B7.1和B7.2/B70。尽管有这些观察结果，但T细胞通常不被认为具有专职APC的作用，因为在未添加专职APC的情况下，TCC呈递抗原后观察到的是反应性T细胞无反应，而非增殖。在此，我们表明，在用游离SAg刺激后，TCC会发生增殖反应，在培养1周后，会出现对T细胞受体（TCR）介导的刺激无反应，但对白介素-2有反应的SAg依赖性无反应状态。添加自体爱泼斯坦-巴尔病毒（EBV）转化的B细胞并不能阻止SAg诱导的无反应状态，这表明在传统APC存在的情况下也会发生无反应状态的诱导。相反，如果TCC受到预先用SAg脉冲处理的辐照APC（EBV或TCC）刺激，则不会观察到无反应状态的诱导。事实上，培养1周后，用结合有SAg的APC刺激的TCC对TCR介导的刺激有反应，而与用于SAg呈递的APC（EBV或TCC）无关。在防止T-T细胞接触的半固体培养基中用游离SAg刺激TCC会导致激活，随后进入无反应状态，这表明无反应状态是单个T细胞水平上SAg识别的结果。这些数据表明，在可溶性SAg存在下培养1周后TCC中观察到的无反应状态并非TCC固有地无法作为专职APC的结果。相反，这种现象取决于可溶性SAg的存在，导致T细胞自身刺激。
