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感染SIVmac251或猿猴-人类免疫缺陷病毒KU2的猕猴黏膜中具有功能的猿猴免疫缺陷病毒Gag特异性CD8 +上皮内淋巴细胞

Functional simian immunodeficiency virus Gag-specific CD8+ intraepithelial lymphocytes in the mucosae of SIVmac251- or simian-human immunodeficiency virus KU2-infected macaques.

作者信息

Stevceva Liljana, Moniuszko Marcin, Alvarez Xavier, Lackner Andrew A, Franchini Genoveffa

机构信息

Basic Research Laboratory, National Cancer Institute, 41/D804, Bethesda, MD 20892-5055, USA.

出版信息

Virology. 2004 Feb 20;319(2):190-200. doi: 10.1016/j.virol.2003.08.046.

DOI:10.1016/j.virol.2003.08.046
PMID:14980480
Abstract

The vaginal and rectal mucosae are the first line of cellular immune defense to sexually transmitted human immunodeficiency virus type 1 (HIV-1) entry. Thus, intraepithelial lymphocytes (IELs) may be important in the immune response to HIV infection. Here we investigated whether functional IELs in mucosal compartments could be visualized by direct staining with a tetrameric complex specific for the simian immunodeficiency virus (SIV) immunodominant Gag epitope in either separated IEL cells or tissues of macaques infected with SIVmac251. Of the 15 Mamu-A*01-positive macaques studied here, eight were chronically infected with either SIVmac251 or simian-human immunodeficiency virus (SHIV) KU2 and the remaining seven were exposed mucosally to SIVmac251 and sacrificed within 48 h to assess the local immune response. Gag-specific CD8+ T-cells were found in separated IELs from the rectum, colon, jejunum, and vagina of most infected animals. Direct staining of tetramers also revealed their presence in intact tissue. These Gag-specific IELs expressed the activation marker CD69 and produced IFN-gamma, suggesting an active immune response in this locale.

摘要

阴道和直肠黏膜是抵御性传播的1型人类免疫缺陷病毒(HIV-1)侵入的细胞免疫防御的第一道防线。因此,上皮内淋巴细胞(IELs)在对HIV感染的免疫反应中可能很重要。在此,我们研究了在感染SIVmac251的猕猴的分离IEL细胞或组织中,是否可以通过用对猿猴免疫缺陷病毒(SIV)免疫显性Gag表位特异的四聚体复合物直接染色来观察黏膜区室中的功能性IELs。在我们研究的15只Mamu-A*01阳性猕猴中,8只长期感染SIVmac251或猿猴-人类免疫缺陷病毒(SHIV)KU2,其余7只经黏膜暴露于SIVmac251,并在48小时内处死以评估局部免疫反应。在大多数受感染动物的直肠、结肠、空肠和阴道的分离IELs中发现了Gag特异性CD8+T细胞。四聚体的直接染色还揭示了它们在完整组织中的存在。这些Gag特异性IELs表达激活标志物CD69并产生γ干扰素,表明在该部位存在活跃的免疫反应。

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