Gastrointestinal-associated lymphoid tissue immune reconstitution in a randomized clinical trial of raltegravir versus non-nucleoside reverse transcriptase inhibitor-based regimens
Gastrointestinal-associated lymphoid tissue immune reconstitution in a randomized clinical trial of raltegravir versus non-nucleoside reverse transcriptase inhibitor-based regimens
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DOI：
10.1097/qad.0b013e3283546595
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发表时间：
2012-08-24
期刊：
影响因子：
3.8
通讯作者：
Pollard, Richard B.
中科院分区：
文献类型：
--
作者：
Asmuth, David M.;Ma, Zhong-Min;Pollard, Richard B.
目的：检查随机接受不同治疗方案的慢性 HIV 感染患者十二指肠组织中的免疫恢复以及免疫激活减少的相关性。设计：随机临床试验 (RCT)，比较拉替拉韦与基于非核苷逆转录酶抑制剂的方案，两者均采用固定剂量替诺福韦二富马酸/恩曲他滨。方法：抗逆转录病毒 未接受过 ART 治疗的志愿者在治疗 9 个月之前和之后接受了上消化道内窥镜检查以进行十二指肠活检。将组织石蜡包埋用于免疫组织化学或消化成单细胞悬液用于淋巴细胞亚群和激活表型的流式细胞术。测量血浆可溶性 CD14 水平作为细菌易位的替代指标。结果：16 名 HIV 阳性个体和 7 名对照个体完成了研究程序。观察到十二指肠固有层 CD4(+) T 细胞数量小幅增加，特别是相对于对照志愿者群体而言，治疗组之间没有差异。 CD4（+）T细胞百分比的增加主要是由于CD8（+）T细胞数量的下降，与外周血和对照相比，CD8（+）T细胞数量不成比例地增加。随机分配至拉替拉韦组的患者十二指肠组织固有层中的 sCD14 水平和 CD8(+) T 细胞数量持续下降。结论：第一个关于十二指肠组织中淋巴细胞群恢复的随机对照试验表明，与仅考虑 CD3/CD4 百分比相比，治疗前 9 个月期间 CD4(+) T 细胞数量的增加更为温和。尽管 ART 9 个月后有所减少，但十二指肠胃肠相关淋巴组织 (GALT) 中的 CD8 数量仍然不成比例地增加。局部而非全身抗原刺激似乎驱动了 GALT 中 CD8(+) T 淋巴细胞的扩增。除了病毒诱导的 CD8 扩增之外的因素也可能导致这种局部免疫反应。 (C) 2012 年 Wolters Kluwer Health 垂直条 Lippincott Williams & Wilkins
Objectives: To examine immune restoration in duodenal tissue and correlates of reduction of immune activation in chronic HIV-infected patients randomized to different treatment regimens.Design: Randomized clinical trial (RCT) comparing raltegravir to a non-nucleoside reverse transcriptase inhibitor-based regimen, both with fixed-dose tenofovir difumerate/emtricitabine.Methods: Antiretroviral therapy (ART)-naive volunteers underwent upper endoscopy for duodenal biopsies before and after 9 months of therapy. Tissue was paraffin-embedded for immunohistochemistry or digested into single-cell suspensions for flow cytometry of lymphocyte subsets and activation phenotype. Plasma-soluble CD14 levels were measured as a surrogate for bacterial translocation.Results: Sixteen HIV-positive and seven control individuals completed study procedures. Small increases in duodenal lamina propria CD4(+) T-cell numbers were observed, especially when viewed relative to populations in control volunteers, with no differences between treatment arms. The increase in CD4(+) T-cell percentage was due largely to declines in CD8(+) T-cell numbers, which were disproportionately increased compared to peripheral blood and controls. Patients randomized to the raltegravir arm had consistent declines in both sCD14 levels and CD8(+) T-cell numbers in the duodenal tissue lamina propria.Conclusions: This first RCT of lymphocyte population restoration in duodenal tissue demonstrates more modest increases in CD4(+) T-cell numbers during the first 9 months of therapy than when considering CD3/CD4 percentages only. Although reduced after 9 months of ART, disproportional increased CD8 populations persist in duodenal gastrointestinal-associated lymphoid tissue (GALT). Local rather than systemic antigenic stimulation appears to be driving expanded CD8(+) T lymphocytes in GALT. Factors other than viral-induced CD8 expansion may be contributing to this local immunologic response. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins