Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy.
Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy.
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DOI：
10.1084/jem.190.5.725
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发表时间：
1999-09-06
期刊：
影响因子：
--
通讯作者：
Ho DD
中科院分区：
文献类型：
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作者：
Zhang L;Lewin SR;Markowitz M;Lin HH;Skulsky E;Karanicolas R;He Y;Jin X;Tuttleton S;Vesanen M;Spiegel H;Kost R;van Lunzen J;Stellbrink HJ;Wolinsky S;Borkowsky W;Palumbo P;Kostrikis LG;Ho DD
胸腺在HIV-1发病机制中的作用尚不清楚。我们开发了一种基于检测T细胞受体重排的主要切除DNA副产物（称为α1环）来定量血液中最近胸腺移出物数量的测定法。通过对532名正常人的研究发现，血液中α1环的数量在10-15岁之间保持较高水平，在青少年后期急剧下降，此后逐渐下降。与年龄匹配的未感染对照个体相比，HIV-1感染成人的α1环数显著减少;然而，有许多个体的α1环数正常。在74名接受高效抗逆转录病毒治疗的患者中，我们发现基线值已经在正常范围内的患者对α1环数没有明显影响，但在先前存在损伤的患者中观察到显著增加。然而，α1环数量的增加在数值上不足以解释初始T淋巴细胞水平的升高。总体而言，很难将胸腺再生衰竭作为HIV-1感染中CD 4淋巴细胞耗竭的一般机制，因为α1环数在相当一部分HIV-1感染个体中是正常的。
The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed α1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that α1 circle numbers in blood remain high for the first 10–15 yr of life, a sharp drop is seen in the late teen years, and a gradual decline occurs thereafter. Compared with age-matched uninfected control individuals, α1 circle numbers in HIV-1–infected adults were significantly reduced; however, there were many individuals with normal α1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on α1 circle numbers in those whose baseline values were already within the normal range, but significant increases were observed in those with a preexisting impairment. The increases in α1 circle numbers were, however, numerically insufficient to account for the rise in levels of naive T lymphocytes. Overall, it is difficult to invoke thymic regenerative failure as a generalized mechanism for CD4 lymphocyte depletion in HIV-1 infection, as α1 circle numbers are normal in a substantial subset of HIV-1–infected individuals.