Anergy and apoptosis in CD8+ T cells from HIV-infected persons.
Anergy and apoptosis in CD8+ T cells from HIV-infected persons.
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DOI：
10.4049/jimmunol.153.1.412
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发表时间：
1994-07
影响因子：
4.4
通讯作者：
Dorothy E. Lewis;D. N. Tang;A. Adu-Oppong;Wendy Schober;J. Rodgers
中科院分区：
文献类型：
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作者：
Dorothy E. Lewis;D. N. Tang;A. Adu-Oppong;Wendy Schober;J. Rodgers
HIV感染者的CD8+T细胞在感染早期增加，表现为激活AGS水平升高，并具有异常的MHC限制性、HIV特异性和非特异性细胞毒能力。矛盾的是，这些细胞在体外也对T细胞信号没有反应，并降低了体外克隆的潜力。HIV特异性CTL前体也在感染后期丢失。一项定量的Southern印迹技术显示，来自无症状的HIV感染者的CD8+T细胞在隔夜孵育后DNA片断增加。核酸内切酶抑制剂可以减少DNA片段化，但放线菌酮不能减少DNA片段化，这表明体内存在凋亡前状态。加入IL-2也可部分抑制DNA片段化。尽管只有不表达活化AGS(DR-、CD28+、CD57-表型)的CD8+T细胞在IL-2中孵育时，CD8+T细胞的碎片减少，但在HIV感染者的CD8+亚群中没有观察到一致的差异。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-细胞的一部分不会增殖为T细胞信号，这些来自对照组的细胞在体外培养3天后显示DNA片段化增加，无论刺激条件如何。这表明这些细胞是终末期细胞。综上所述，这些数据表明艾滋病毒感染者中无能或凋亡的CD8+T细胞增加。HIV特异性CD8+T细胞的最终耗尽可能通过增殖、无能诱导和凋亡的过程发生。
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.