分化改变是HIV特异性CD4+T细胞功能障碍的核心

　　科学家近期发现在进行性疾病中，分化改变是HIV特异性CD4+T细胞功能障碍的核心。这一成果由蒙特拉尔大学医院中心研究中心Daniel E. Kaufmann课题组取得，发表在2019年8月出版的《自然-免疫学》杂志上。

　　该团队在HIV感染者接受抗逆转录病毒治疗(ART)前后对对他们进行了CD4+ T细胞进行了提取，并且对所提取的细胞进行了全基因组的转录和功能分析。发现HIV特异性的CD4+ T细胞的类卵泡辅助T细胞(TFH)的特征表明它们已经被病毒所感染。从主动抵抗艾滋病毒病人(接受“精英控制者”药治疗)中提取的艾滋病毒特异性CD4+ T细胞强烈地表达与辅助性T细胞的TH1、TH17和TH22亚群相关的基因。通过抗逆转录病毒疗法对病毒抑制的情况不同，虽然与TFH细胞相关的基因表达减少了，但与施用“精英控制者”的情况相比，与TH1、TH17和TH22细胞相关的基因表达持续较低。因此，分化改变是艾滋病毒特异性CD4+ T细胞损伤的核心，涉及功能的获得和功能的丧失。

　　据介绍，人们对慢性人类感染中病毒特异性CD4+ T细胞的功能障碍知之甚少。

　　附：英文原文

　　Title: Altered differentiation is central to HIV-specific CD4 + T cell dysfunction in progressive disease

　　Author: Antigoni Morou, Elsa Brunet-Ratnasingham, Mathieu Dub, Roxanne Charlebois, Eloi Mercier, Sam Darko, Nathalie Brassard, Krystelle Nganou-Makamdop, Sahaana Arumugam, Gabrielle Gendron-Lepage, Lifei Yang, Julia Niessl, Amy E. Baxter, James M. Billingsley, Premeela A. Rajakumar, Franois Lefebvre, R. Paul Johnson, Ccile Tremblay, Jean-Pierre Routy, Richard T. Wyatt, Andrs Finzi, Daniel C. Douek, Daniel E. Kaufmann

　　Issue & Volume: Volume 20 Issue 8

　　Abstract: Dysfunction of virus-specific CD4+ T cells in chronic human infections is poorly understood. We performed genome-wide transcriptional analyses and functional assays of CD4+ T cells specific for human immunodeficiency virus (HIV) from HIV-infected people before and after initiation of antiretroviral therapy (ART). A follicular helper T cell (TFH cell)-like profile characterized HIV-specific CD4+ T cells in viremic infection. HIV-specific CD4+ T cells from people spontaneously controlling the virus (elite controllers) robustly expressed genes associated with the TH1, TH17 and TH22 subsets of helper T cells. Viral suppression by ART resulted in a distinct transcriptional landscape, with a reduction in the expression of genes associated with TFH cells, but persistently low expression of genes associated with TH1, TH17 and TH22 cells compared to the elite controller profile. Thus, altered differentiation is central to the impairment of HIV-specific CD4+ T cells and involves both gain of function and loss of function.

　　DOI: 10.1038/s41590-019-0418-x

　　Source: https://www.nature.com/articles/s41590-019-0418-x

　　期刊信息

　　Nature Immunology：《自然-免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：23.53
　　官方网址：https://www.nature.com/ni/
　　投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex

　　(来源：科学网 小柯机器人)