Shortened telomeres in the expanded CD28- CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis
Shortened telomeres in the expanded CD28- CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis
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DOI：
10.1097/00002030-199607000-00001
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发表时间：
1996-07-01
期刊：
影响因子：
3.8
通讯作者：
Giorgi, JV
中科院分区：
文献类型：
--
作者：
Effros, RB;Allsopp, R;Giorgi, JV
目的：为了验证这一假设，即在HIV疾病中非增殖性CD 28-CD 8 + T细胞的扩增群体缩短了端粒，从而提供证据表明在HIV疾病期间发生的CD 8+细胞分裂的增加轮次，可能导致复制性衰老和CD 8 + T细胞应答的耗尽。在晚期HIV疾病中，已经记录了具有降低的增殖潜力的CD 28-CD 8+细胞的扩增群体。一个类似的人口的CD 28-CD 8+细胞已被确定在老龄化的人，端粒长度的测量表明，这些细胞已经达到了不可逆的状态复制senescence.Methods：CD 8+细胞从HIV感染者和对照受试者通过流式细胞仪分选成CD 28+和CD 28-馏分。结果：HIV感染者CD 28-CD 8+细胞的端粒长度在5 ~ 7 kb之间，明显短于未感染者CD 28-CD 8+细胞的端粒长度（P = 0.003）。从HIV感染者的CD 28-CD 8+细胞中的TRF长度是相同的百岁老人外周血单核细胞观察到的，是兼容的复制senescence.Conclusions的状态：缩短端粒的CD 28-CD 8+细胞中的HIV感染者和这些细胞的增殖能力差的识别CD 8+细胞复制衰老作为一个新的特征的HIV疾病。我们的研究结果提供了一种机制，为CD 8+细胞控制的病毒复制的损失，伴随着先进的艾滋病毒疾病。复制性衰老可能导致慢性HIV疾病导致的T细胞反应衰竭。这种现象是否发生在其他慢性病毒感染中尚不清楚。
Objective: To test the hypothesis that the expanded population of non-proliferative CD28-CD8+ T cells in HIV disease have shortened telomeres, thereby providing evidence that increased rounds of CD8+ cell division occur during HIV disease, possibly leading to replicative senescence and exhaustion of CD8+ T-cell responses.Design: CD8+ cells play a central role in control of HIV infection. In late HIV disease, an expanded population of CD28- CD8+ cells with reduced proliferative potential has been documented. A similar population of CD28- CD8+ cells has been identified in ageing humans, where telomere length measurements have suggested that these cells have reached the irreversible state of replicative senescence.Methods: CD8+ cells from HIV-infected and control subjects were sorted by flow cytometry into CD28+ and CD28- fractions. Telomere lengths were determined as mean terminal restriction fragment (TRF) lengths by Southern hybridization.Results: The TRF lengths of sorted CD28- CD8+ cells in HIV-infected subjects ranged between 5 and 7 kilobases (kb) and were significantly shorter than TRF lengths of CD28- CD8+ cells in uninfected subjects (P = 0.003). The TRF length in CD28- CD8+ cells from HIV-infected subjects was the same as that observed for centenarian peripheral blood mononuclear cells and is compatible with a state of replicative senescence.Conclusions: The shortened telomeres in the CD28- CD8+ cells in HIV-infected subjects and the poor proliferative potential of these cells identifies CD8+ cell replicative senescence as a newly described feature of HIV disease. Our results provide a mechanism for the loss of CD8+ cell control of viral replication that accompanies advanced HIV disease. Replicative senescence may contribute to exhaustion of the T-cell response as a result of chronic HIV disease. Whether this phenomenon occurs in other chronic viral infections is unknown.