Programmed cell death in peripheral lymphocytes from HIV-infected persons: increased susceptibility to apoptosis of CD4 and CD8 T cells correlates with lymphocyte activation and with disease progression.
Programmed cell death in peripheral lymphocytes from HIV-infected persons: increased susceptibility to apoptosis of CD4 and CD8 T cells correlates with lymphocyte activation and with disease progression.
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DOI：
10.4049/jimmunol.156.9.3509
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发表时间：
1996-05
影响因子：
4.4
通讯作者：
M. Gougeon;H. Lecoeur;A. Dulioust;M. G. Enouf;M. Crouvoiser;C. Goujard;T. Debord;L. Montagnier
中科院分区：
文献类型：
--
作者：
M. Gougeon;H. Lecoeur;A. Dulioust;M. G. Enouf;M. Crouvoiser;C. Goujard;T. Debord;L. Montagnier
我们对一大群 HIV 感染者进行了为期 3 年的跟踪，分析了外周淋巴细胞凋亡敏感性增加的潜在原因。通过使用定量细胞荧光法，我们证明在两组供体中，所有淋巴细胞群都对细胞凋亡群做出了成比例的贡献，但在 HIV 感染者中，参与该细胞死亡过程的 T 细胞和 B 细胞的百分比显着增加。为了研究 HIV 感染中细胞凋亡增加与免疫系统激活状态之间的关系，我们分析了凋亡和非凋亡细胞上激活标记的细胞表面表达。我们发现，在HIV感染的慢性期，50%到60%的凋亡细胞表现出激活的表型（它们是HLA-DR+、CD38+、CD45RO+和Fas+），有趣的是，CD45RO+亚群在HIV阳性者中似乎更容易发生凋亡。这项研究还表明，在凋亡细胞上发现的激活表型并不是患者淋巴细胞的显着特征，因为它在凋亡细胞中与对照淋巴细胞中的比例相似。然而，我们发现 HIV 感染者的 CD4 和 CD8 T 细胞中抗 CD3 诱导的细胞凋亡强度与其体内 CD45RO 和 HLA-DR 分子的表达之间存在显着相关性。最后，发现总淋巴细胞自发性或抗 CD3 诱导的细胞凋亡强度与疾病进展之间存在显着相关性。当分别分析 CD4 和 CD8 T 细胞亚群时，这一点得到了证实。总之，这些观察结果表明，HIV 感染者外周 T 细胞凋亡的敏感性增加与疾病进展相关，并支持这样的假设：在 HIV 感染过程中发生的免疫系统的慢性激活是导致这种细胞缺失过程的主要机制。
We analyzed the potential causes of the increased susceptibility to apoptosis of peripheral lymphocytes from a large cohort of HIV-infected persons that we followed during a 3-yr period. By using quantitative cytofluorometric methods, we demonstrate that all lymphocyte populations were contributing proportionally to the apoptotic population in both groups of donors, but the percentage of T and B cells involved in this cell death process was significantly increased in HIV-infected persons. To study the relationship between the increased apoptosis in HIV infection and the activation state of the immune system, we analyzed cell surface expression of activation markers on apoptotic and nonapoptotic cells. We found that in the chronic phase of HIV infection, 50 to 60% of the apoptotic cells exhibited an activated phenotype (they were HLA-DR+, CD38+, CD45RO+, and Fas+), and interestingly, the CD45RO+ subset appeared to be more prone to apoptosis in HIV-positive persons. This study also indicates that the activated phenotype found on apoptotic cells was not a distinctive feature of patients' lymphocytes since it was in similar proportion in apoptotic cells from control lymphocytes. However, a significant correlation was found between the intensity of anti-CD3-induced apoptosis in both CD4 and CD8 T cells from HIV-infected persons and their in vivo expression of CD45RO and HLA-DR molecules. Finally, a significant correlation was found between the intensity of spontaneous or anti-CD3-induced apoptosis in total lymphocytes and disease progression; this was confirmed when the CD4 and CD8 T cell subsets were analyzed separately. Altogether these observations indicate that the increased susceptibility to apoptosis of peripheral T cells from HIV-infected persons correlates with disease progression and support the hypothesis that the chronic activation of the immune system occurring throughout HIV infection is the primary mechanism responsible for this cell deletion process.