Multiparameter evaluation of human thymic function: interpretations and caveats

Multiparameter evaluation of human thymic function: interpretations and caveats
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DOI:
10.1016/j.clim.2004.12.008
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发表时间:
2005-05-01
影响因子:
8.6
通讯作者:
McCune, JM
McCune, JM
中科院分区:
医学3区
文献类型:
--
作者:
Harris, JM;Hazenberg, MD;McCune, JM

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在提供高效抗逆转录病毒疗法(HAART)之后,许多感染I型人类免疫缺陷病毒(HIV)的成年人循环中的CD4 + T细胞水平升高。为了研究免疫重建所涉及的因素,我们通过CT扫描测量了胸腺的丰度,通过流式细胞术测量了循环中的初始表型CD4 + T细胞,并通过定量PCR测量了40名病毒学抑制的HIV感染成年人和33名年龄匹配的未感染HIV的对照者的T细胞受体(TCR)重排切除环(TRECs)。在未感染HIV的受试者中,正如预期的那样,初始T细胞数量、胸腺丰度以及携带TRECs的循环初始CD4 + T细胞的频率随年龄增长而下降。当针对这种与年龄的关系进行校正后,初始T细胞数量与初始T细胞TREC频率显著相关。病毒学抑制的HIV感染受试者具有更高的TREC频率,并且与年龄匹配的未感染HIV的成年人相比,39岁以上的受试者更有可能具有丰富的胸腺。然而,无论胸腺大小、年龄或TREC频率如何,所有HIV感染受试者的初始T细胞绝对数量都减少了。这些数据说明了这些胸腺大小和功能测量指标之间的复杂关系,并强调了未来需要开发更明确的胸腺功能测量方法。(c)2004爱思唯尔公司。保留所有权利。
After the provision of highly active antiretroviral therapy (HAART), the level of circulating CD4+ T cells increases in many adults infected with the human immunodeficiency virus, type I (HIV). To study factors involved in immune reconstitution, we have measured thymic abundance by CT scans, circulating naive-phenotype CD4+ T cells by flow cytometry, and T cell receptor (TCR) rearrangement excision circles (TRECs) by quantitative PCR in 40 virologically suppressed, HIV-infected adults and 33 age-matched, HIV-uninfected controls. In HIV-uninfected subjects, naive T cell numbers, thymic abundance, and the frequency of circulating naive CD4+ T cells hearing TRECs decreased with age, as expected. When corrected for this relationship with age, naive T cell numbers correlated significantly with naive T cell TREC frequencies. Virologically suppressed HIV-infected subjects had higher TREC frequencies, and subjects over the age of 39 were more likely to have abundant thymus compared to age-matched, HIV-uninfected adults. Nevertheless, all HIV-infected subjects had reduced absolute numbers of naive T cells, irrespective of thymic size, age, or TREC frequencies. These data illustrate the complex relationship between these measures of thymic size and function and underscore the need to develop more definitive measures of thymic function in the future. (c) 2004 Elsevier Inc. All rights reserved.