Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract.
Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract.
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DOI：
10.1084/jem.20041196
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发表时间：
2004-09-20
期刊：
影响因子：
--
通讯作者：
Markowitz M
中科院分区：
文献类型：
--
作者：
Mehandru S;Poles MA;Tenner-Racz K;Horowitz A;Hurley A;Hogan C;Boden D;Racz P;Markowitz M
鉴于胃肠道 (GI) 粘膜中含有表达 CCR5、免疫激活的 CD4+ T 细胞，因此特别容易受到人类免疫缺陷病毒 (HIV)-1 感染。我们进行这项研究是为了评估在初次感染期间，HIV-1 感染者中是否会观察到粘膜 CD4+ T 细胞的优先消耗，检查这些细胞被消耗的解剖亚区室，并检查抑制性高活性抗逆转录病毒治疗是否可以导致粘膜区室的完全免疫重建。我们的结果表明，在原发性 HIV-1 感染期间，与外周血 CD4+ T 细胞相比，粘膜 CD4+ T 细胞显着且优先减少。 CD4+ T 细胞损失主要发生在胃肠道粘膜的效应子区室中，这与存在 HIV-1 RNA 的诱导区室不同。对一组原发性 HIV-1 感染受试者的横断面分析表明，尽管长期抑制 HIV-1 可使外周血 CD4+ T 细胞群几乎完全免疫恢复，但胃肠道粘膜中 CD4+ T 细胞的损失量仍显着增加，尽管进行了长达 5 年的完全抑制治疗。鉴于粘膜区室在 HIV-1 发病机制中的重要性，进一步研究以阐明此处观察到的变化的重要性至关重要。
Given its population of CCR5-expressing, immunologically activated CD4+ T cells, the gastrointestinal (GI) mucosa is uniquely susceptible to human immunodeficiency virus (HIV)-1 infection. We undertook this study to assess whether a preferential depletion of mucosal CD4+ T cells would be observed in HIV-1–infected subjects during the primary infection period, to examine the anatomic subcompartment from which these cells are depleted, and to examine whether suppressive highly active antiretroviral therapy could result in complete immune reconstitution in the mucosal compartment. Our results demonstrate that a significant and preferential depletion of mucosal CD4+ T cells compared with peripheral blood CD4+ T cells is seen during primary HIV-1 infection. CD4+ T cell loss predominated in the effector subcompartment of the GI mucosa, in distinction to the inductive compartment, where HIV-1 RNA was present. Cross-sectional analysis of a cohort of primary HIV-1 infection subjects showed that although chronic suppression of HIV-1 permits near-complete immune recovery of the peripheral blood CD4+ T cell population, a significantly greater CD4+ T cell loss remains in the GI mucosa, despite up to 5 yr of fully suppressive therapy. Given the importance of the mucosal compartment in HIV-1 pathogenesis, further study to elucidate the significance of the changes observed here is critical.
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