Gougeon M L, Lecoeur H, Dulioust A, Enouf M G, Crouvoiser M, Goujard C, Debord T, Montagnier L
Viral Oncology Unit, Department of AIDS and Retrovirus, Pasteur Institute, Paris, France.
J Immunol. 1996 May 1;156(9):3509-20.
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.
我们分析了一大群在3年期间接受随访的HIV感染者外周淋巴细胞凋亡易感性增加的潜在原因。通过使用定量细胞荧光分析方法，我们证明在两组供体中所有淋巴细胞亚群对凋亡细胞群体的贡献成比例，但参与这一细胞死亡过程的T细胞和B细胞百分比在HIV感染者中显著增加。为了研究HIV感染中凋亡增加与免疫系统激活状态之间的关系，我们分析了凋亡细胞和非凋亡细胞上激活标志物的细胞表面表达。我们发现，在HIV感染的慢性期，50%至60%的凋亡细胞表现出激活表型（它们是HLA-DR+、CD38+、CD45RO+和Fas+），有趣的是，CD45RO+亚群在HIV阳性个体中似乎更容易发生凋亡。这项研究还表明，凋亡细胞上发现的激活表型不是患者淋巴细胞的独特特征，因为在对照淋巴细胞的凋亡细胞中其比例相似。然而，在HIV感染者的CD4和CD8 T细胞中，抗CD3诱导的凋亡强度与其体内CD45RO和HLA-DR分子的表达之间存在显著相关性。最后，在总淋巴细胞中自发或抗CD3诱导的凋亡强度与疾病进展之间存在显著相关性；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细胞凋亡易感性增加与疾病进展相关，并支持这样一种假说，即整个HIV感染过程中发生的免疫系统慢性激活是导致这种细胞缺失过程的主要机制。
