Enhanced levels of functional HIV-1 co-receptors on human mucosal T cells demonstrated using intestinal biopsy tissue

Enhanced levels of functional HIV-1 co-receptors on human mucosal T cells demonstrated using intestinal biopsy tissue
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DOI:
10.1097/00002030-200008180-00011
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发表时间:
2000-08-18
期刊:
影响因子:
3.8
通讯作者:
Giorgi, JV
Giorgi, JV
中科院分区:
医学2区
文献类型:
--
作者:
Anton, PA;Elliott, J;Giorgi, JV

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目的:应用胃镜活检方法检测血液和肠道组织中CD4细胞表面共受体表达的差异。设计:比较健康对照组黏膜和外周血中CD4T细胞的协同受体表达和感染HIV-1的易感性。方法:采用流式细胞术对胃镜活检分离的黏膜和健康对照血液中分离的CD4T细胞表面CCR5和CXCR4的表达进行定量。通过检测p24来评估对R5和X4菌株体外感染的易感性。结果:活检获得了足够的淋巴细胞,用于流式细胞仪鉴定和感染性研究。粘膜中表达CCR5的CD4T淋巴细胞百分率和每细胞表达CCR5的细胞数均显著高于外周血CD4T淋巴细胞。CXCR4主要表达于两个隔室的CD4+淋巴细胞上。在体外,粘膜单个核细胞感染R5和X4毒株比外周血单核细胞支持更多的病毒复制。结论:正常肠粘膜中CD4淋巴细胞上CXCR4和CCR5表达增强预示着对R5和X4 HIV-1感染的易感性增加。内窥镜活检提供了一种有用的粘膜组织采样技术,以确定HIV-1可能利用的间隔免疫差异来确定最初的粘膜感染。(C)2000年Lippincott Williams&Wilkins。
Objective: To examine compartmental differences in co-receptor expression on CD4 lymphocytes between blood and gut using endoscopic biopsies.Design: Mucosal and peripheral CD4 T cells from healthy controls were compared For co-receptor expression and vulnerability to infection by HIV-1.Methods: Expression of CCR5 and CXCR4 was quantified by flow cytometry on isolated mucosal CD4 lymphocytes obtained from endoscopic biopsies and blood from healthy controls. Vulnerability to in vitro infection by both R5 and X4 strains was assessed by measuring p24.Results: Biopsies yielded sufficient lymphocytes for flow cytometric characterization and infectivity studies. The percentage of mucosal CD4 T lymphocytes that expressed CCR5 and the per cell expression of CCR5 were both significantly increased compared with that in peripheral blood CD4 T lymphocytes. CXCR4 was expressed on the majority of CD4, lymphocytes in both compartments. In vitro infection of mucosal mononuclear cells supported greater viral replication of both R5 and X4 strains than peripheral blood mononuclear cells.Conclusions: Enhanced expression of CXCR4 and CCR5 on CD4 lymphocytes in normal intestinal mucosa predicts increased vulnerability to infection by both R5 and X4 HIV-1. Endoscopic biopsies provide a useful mucosal tissue sampling technique to identify compartmental immunologic differences that may be exploited by HIV-1 in establishing initial mucosal infection. (C) 2000 Lippincott Williams & Wilkins.