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Detection of HIV-1-specific gastrointestinal tissue resident CD8+ T-cells in chronic infection.
Mucosal Immunology ( IF 8 ) Pub Date : 2018-05-01 , DOI: 10.1038/mi.2017.96
Brenna E Kiniry 1 , Shengbin Li 2 , Anupama Ganesh 1 , Peter W Hunt 3 , Ma Somsouk 4 , Pamela J Skinner 2 , Steven G Deeks 5 , Barbara L Shacklett 1, 6
Affiliation  

Tissue-resident memory (TRM) CD8+ T-cells are non-recirculating, long-lived cells housed in tissues that can confer protection against mucosal pathogens. Human immunodeficiency virus-1 (HIV-1) is a mucosal pathogen and the gastrointestinal tract is an important site of viral pathogenesis and transmission. Thus, CD8+ TRM cells may be an important effector subset for controlling HIV-1 in mucosal tissues. This study sought to determine the abundance, phenotype, and functionality of CD8+ TRM cells in the context of chronic HIV-1 infection. We found that the majority of rectosigmoid CD8+ T-cells were CD69+CD103+S1PR1- and T-betLowEomesoderminNeg, indicative of a tissue-residency phenotype similar to that described in murine models. HIV-1-specific CD8+ TRM responses appeared strongest in individuals naturally controlling HIV-1 infection. Two CD8+ TRM subsets, distinguished by CD103 expression intensity, were identified. CD103Low CD8+ TRM primarily displayed a transitional memory phenotype and contained HIV-1-specific cells and cells expressing high levels of Eomesodermin, whereas CD103High CD8+ TRM primarily displayed an effector memory phenotype and were EomesoderminNeg. These findings suggest a large fraction of CD8+ T-cells housed in the human rectosigmoid mucosa are tissue-resident and that TRM contribute to the anti-HIV-1 immune response. Further exploration of CD8+ TRM will inform development of anti-HIV-1 immune-based therapies and vaccines targeted to the mucosa.

中文翻译:

慢性感染中 HIV-1 特异性胃肠道组织常驻 CD8+ T 细胞的检测。

组织驻留记忆 (T RM ) CD8 + T 细胞是非循环的长寿命细胞,存在于组织中,可提供针对粘膜病原体的保护。人类免疫缺陷病毒-1 (HIV-1) 是一种粘膜病原体,胃肠道是病毒发病和传播的重要部位。因此,CD8 + T RM细胞可能是控制粘膜组织中 HIV-1 的重要效应子集。本研究旨在确定慢性 HIV-1 感染背景下 CD8 + T RM细胞的丰度、表型和功能。我们发现大多数直肠乙状结肠 CD8 + T 细胞是 CD69 + CD103 +S1PR1 -和 T-bet Low Eomesodermin Neg,表明组织驻留表型类似于小鼠模型中描述的表型。HIV-1 特异性 CD8 + T RM反应在自然控制 HIV-1 感染的个体中表现最强。鉴定了两个通过 CD103 表达强度区分的CD8 + T RM子集。CD103 Low CD8 + T RM主要显示过渡记忆表型并包含 HIV-1 特异性细胞和表达高水平 Eomesodermin 的细胞,而 CD103 High CD8 + T RM主要表现出效应记忆表型并且是 Eomesodermin Neg。这些发现表明,人类直肠乙状结肠粘膜中的大部分 CD8 + T 细胞是组织驻留的,并且 T RM有助于抗 HIV-1 免疫反应。进一步探索 CD8 + T RM将为针对粘膜的抗 HIV-1 免疫疗法和疫苗的开发提供信息。
更新日期:2017-12-15
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