In vivo analysis of Fas/FasL interactions in HIV-infected patients
In vivo analysis of Fas/FasL interactions in HIV-infected patients
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DOI：
10.1172/jci2691
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发表时间：
1998-07-01
影响因子：
15.9
通讯作者：
Paya, CV
中科院分区：
文献类型：
--
作者：
Badley, AD;Dockrell, DH;Paya, CV
最近对HIV复制的药理学控制和外周T细胞稳态的分子机制的了解使我们能够在体内研究HIV感染患者中介导T细胞耗竭的机制。在开始高效抗逆转录病毒治疗（HAART）之前，存在高度的淋巴组织凋亡，其在HAART开始后减少（P < 0.001），并与病毒载量的降低和外周血T淋巴细胞的增加直接相关由于Fas/FasL相互作用在外周血T淋巴细胞稳态中起着关键作用，我们研究了HAART前和HAART期间外周血T淋巴细胞对Fas介导的凋亡的敏感性和淋巴组织中的Fast表达。HAART前外周血CD 4 T淋巴细胞中发现的高水平的Fas敏感性在HAART后显著降低，HAART后病毒载量下降（P = 0.018），外周血CD 4 T淋巴细胞计数升高（P <0.01）。但HAART后HIV感染者淋巴组织中增加的Fast表达并没有减少。这些结果表明，淋巴组织细胞凋亡与病毒载量和外周血T淋巴细胞数量直接相关，并表明HIV诱导的Fas依赖性细胞凋亡的易感性可能在HIV感染者的T细胞稳态调节中发挥关键作用。
Recent insights into the pharmacological control of HIV replication and the molecular mechanisms of peripheral T cells homeostasis allowed us to investigate in vivo the mechanisms mediating T cell depletion in HIV-infected patients. Before the initiation of highly active antiretroviral therapy (HAART), a high degree of lymphoid tissue apoptosis is present, which is reduced upon HAART initiation (P < 0.001) and directly correlates with reduction of viral load and increases of peripheral T lymphocytes (P < 0.01), Because Fas/FasL interactions play a key role in peripheral T lymphocyte homeostasis, we investigated the susceptibility to Fas-mediated apoptosis in peripheral T lymphocytes and of Fast expression in lymphoid tissue before and during HAART, High levels of Fas-susceptibility found in peripheral CD4 T lymphocytes before HAART were significantly reduced after HAART, coinciding with decreases in viral load (P = 0.018) and increases in peripheral CD4 T lymphocyte counts (P < 0,01), However, the increased Fast expression in the lymphoid tissue of HIV-infected individuals was not reduced after HAART. These results demonstrate that lymphoid tissue apoptosis directly correlates with viral load and peripheral T lymphocyte numbers, and suggest that HIV-induced susceptibility to Fas-dependent apoptosis may play a key role in the regulation of T cell homeostasis in HIV-infected individuals.