Lewis D E, Tang D S, Adu-Oppong A, Schober W, Rodgers J R
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030.
J Immunol. 1994 Jul 1;153(1):412-20.
CD8+T cells from HIV-infected persons increase early in infection, display increased levels of activation Ags, and abnormal MHC-restricted, HIV-specific and nonspecific cytotoxicity abilities. Paradoxically, these cells are also unresponsive to T cell signaling in vitro and have decreased in vitro cloning potential. HIV-specific CTL precursors also are lost late in infection. A quantitative Southern blotting technique showed that CD8+ T cells from asymptomatic, HIV-infected persons have increased DNA fragmentation after overnight incubation. DNA fragmentation was reduced by an endonuclease inhibitor but not by cycloheximide, suggesting that a pre-apoptotic state exists in vivo. Partial inhibition of DNA fragmentation also could be induced by IL-2 addition. No consistent difference in fragmentation was observed among CD8+ subpopulations from HIV-infected individuals, although only CD8+ T cells that did not express activation Ags (DR-, CD28+, CD57- phenotype) showed reduced fragmentation when incubated in IL-2. A dramatic increase in CD8+, CD28- cells was observed in asymptomatic HIV-infected people. A subset of CD8+, CD28- cells in both controls and HIV-infected people do not proliferate to T cell signals, and these cells from controls demonstrate increased DNA fragmentation in vitro after 3 days of incubation, regardless of stimulation conditions. This suggests that the cells are end-stage cells. Taken together, the data suggest an increase in anergic or apoptotic CD8+ T cells in HIV-infected persons. Eventual depletion of HIV-specific CD8+ T cells may occur through a process of proliferation, anergy induction, and apoptosis.
来自HIV感染者的CD8 + T细胞在感染早期数量增加，显示出活化抗原水平升高，以及异常的MHC限制性、HIV特异性和非特异性细胞毒性能力。矛盾的是，这些细胞在体外对T细胞信号也无反应，并且体外克隆潜力降低。HIV特异性CTL前体在感染后期也会丧失。定量Southern印迹技术显示，无症状HIV感染者的CD8 + T细胞在过夜孵育后DNA片段化增加。DNA片段化可被核酸内切酶抑制剂减少，但不能被环己酰亚胺减少，这表明体内存在预凋亡状态。添加IL-2也可部分诱导DNA片段化的抑制。在HIV感染者的CD8 +亚群中未观察到片段化的一致差异，尽管只有不表达活化抗原（DR-、CD28 +、CD57-表型）的CD8 + T细胞在IL-2中孵育时片段化减少。在无症状HIV感染者中观察到CD8 +、CD28-细胞显著增加。在对照组和HIV感染者中，CD8 +、CD28-细胞亚群的一部分对T细胞信号不增殖，并且来自对照组的这些细胞在孵育3天后体外显示出DNA片段化增加，无论刺激条件如何。这表明这些细胞是终末阶段细胞。综上所述，数据表明HIV感染者中无反应性或凋亡性CD8 + T细胞增加。HIV特异性CD8 + T细胞的最终耗竭可能通过增殖、无反应性诱导和凋亡过程发生。
