Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans
Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans
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DOI：
10.1038/4772
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发表时间：
1999-01-01
期刊：
影响因子：
82.9
通讯作者：
McCune, JM
中科院分区：
文献类型：
--
作者：
Hellerstein, M;Hanley, MB;McCune, JM
晚期HIV - 1疾病中T细胞耗竭的动态基础仍存在争议。我们利用一种新的非放射性内源性标记技术（1），对正常人和HIV - 1感染者的循环T细胞动力学进行了直接测量。在健康的HIV - 1血清阴性受试者中，CD4（+）和CD8（+）T细胞的半衰期分别为87天和77天，绝对产生率分别为每天每微升10个CD4（+）T细胞和每天每微升6个CD8（+）T细胞。在未经治疗的HIV - 1感染者（平均CD4水平为每微升342个细胞）中，每个亚群的半衰期不到健康的HIV - 1血清阴性受试者的1/3，并且CD4（+）T细胞的绝对产生率没有增加以作补偿。在高效抗逆转录病毒疗法抑制病毒复制12周后，循环CD4（+）和CD8（+）T细胞的产生率大幅提高；CD4水平升高的动力学基础是循环细胞产生增多，而非半衰期延长。这些直接测量结果表明，CD4（+）T细胞淋巴细胞减少是由于存活时间缩短以及循环CD4（+）T细胞产生未能增加所致。我们的研究结果将注意力集中在HIV - 1疾病发病机制以及抗逆转录病毒疗法应答中的T细胞产生系统上。
The dynamic basis for T-cell depletion in late-stage HIV-1 disease remains controversial. Using a new, non-radioactive, endogenous labeling technique(1), we report direct measurements of circulating T-cell kinetics in normal and in HIV-l-infected humans. In healthy, HIV-l-seronegative subjects, CD4(+) and CD8(+) T cells had half-lives of 87 days and 77 days, respectively, with absolute production rates of 10 CD4(+) T cells/mu l per day and 6 CD8(+) T cells/mu l per day. In untreated HIV-l-infected subjects (with a mean CD4 level of 342 cells/mu l), the half-life of each subpopulation was less than 1/3 as long as those of healthy, HIV-l-seronegative subjects but was not compensated by an increased absolute production rate of CD4(+) T cells. After viral replication was suppressed by highly active antiretroviral therapy for 12 weeks, the production rates of circulating CD4(+) and CD8(+) T cells were considerably elevated; the kinetic basis of increased CD4 levels was greater production, not a longer half-life, of circulating cells. These direct measurements indicate that CD4(+) T-cell lymphopenia is due to both a shortened survival time and a failure to increase the production of circulating CD4(+) T cells. Our results focus attention on T-cell production systems in the pathogenesis of HIV-1 disease and the response to antiretroviral therapy.