Human CD8(+) T cells transduced with an additional receptor bispecific for both Mycobacterium tuberculosis and HIV-1 recognize both epitopes.
Human CD8(+) T cells transduced with an additional receptor bispecific for both Mycobacterium tuberculosis and HIV-1 recognize both epitopes.
复制标题
DOI：
10.1111/jcmm.12878
复制
发表时间：
2016-10
影响因子：
5.3
通讯作者：
Ma L
中科院分区：
文献类型：
--
作者：
Zhou CY;Wen Q;Chen XJ;Wang RN;He WT;Zhang SM;Du XL;Ma L
结核病（TB）和人类免疫缺陷病毒1型（HIV-1）感染密切相关，四分之一的结核病/艾滋病毒合并感染死亡者死于结核病。效应CD 8 + T细胞在控制结核分枝杆菌（MTB）和HIV-1感染中起着至关重要的作用。大量效应CD 8 + T细胞的连续转移是一种有吸引力的策略，可以将改善的抗MTB/HIV-1活性施加到合并感染的个体上。由于异源免疫的广泛存在，即T细胞与由相关甚至非常不相似的病原体编码的肽交叉反应，因此找到识别MTB和HIV-1抗原肽的单个T细胞受体（TCR）是合理的。在本研究中，使用互补决定区3谱型分析从HLA-A *0201+健康个体的外周血单核细胞中筛选出对MTB Ag 85 B199 - 207肽和HIV-1 Env 120 - 128肽均具有特异性的单个TCR，并使用重组逆转录病毒载体将其转移至原代CD 8 + T细胞。TCR基因修饰的CD 8 + T细胞的双特异性通过自体树突状细胞抗原呈递Ag 85 B199 - 207或Env 120 - 128后干扰素-γ、肿瘤坏死因子-α、颗粒酶B的分泌增加和特异性细胞溶解活性来证明。据我们所知，这项研究是第一份报告，提出通过用单个TCR免疫CD 8 + T细胞来同时产生针对MTB和HIV-1的两种不同抗原肽的应答。总之，用额外的双特异性TCR转导的T细胞可能是MTB/HIV-1共感染个体的免疫治疗中的有用策略。
Tuberculosis (TB) and human immunodeficiency virus type 1 (HIV‐1) infection are closely intertwined, with one‐quarter of TB/HIV coinfected deaths among people died of TB. Effector CD8+ T cells play a crucial role in the control of Mycobacterium tuberculosis (MTB) and HIV‐1 infection in coinfected patients. Adoptive transfer of a multitude of effector CD8+ T cells is an appealing strategy to impose improved anti‐MTB/HIV‐1 activity onto coinfected individuals. Due to extensive existence of heterologous immunity, that is, T cells cross‐reactive with peptides encoded by related or even very dissimilar pathogens, it is reasonable to find a single T cell receptor (TCR) recognizing both MTB and HIV‐1 antigenic peptides. In this study, a single TCR specific for both MTB Ag85B199‐207 peptide and HIV‐1 Env120‐128 peptide was screened out from peripheral blood mononuclear cells of a HLA‐A*0201+ healthy individual using complementarity determining region 3 spectratype analysis and transferred to primary CD8+ T cells using a recombinant retroviral vector. The bispecificity of the TCR gene‐modified CD8+ T cells was demonstrated by elevated secretion of interferon‐γ, tumour necrosis factor‐α, granzyme B and specific cytolytic activity after antigen presentation of either Ag85B199‐207 or Env120‐128 by autologous dendritic cells. To the best of our knowledge, this study is the first report proposing to produce responses against two dissimilar antigenic peptides of MTB and HIV‐1 simultaneously by transfecting CD8+ T cells with a single TCR. Taken together, T cells transduced with the additional bispecific TCR might be a useful strategy in immunotherapy for MTB/HIV‐1 coinfected individuals.
登录
查看更多内容
影响因子：
56.9
作者：
Arstila, TP;Casrouge, A;Kourilsky, P
通讯作者：
Kourilsky, P
DOI：
10.1111/j.1440-1843.2010.01739.x
发表时间：
2010-04
期刊：
Respirology (Carlton, Vic.)
影响因子：
--
作者：
Dheda K;Schwander SK;Zhu B;van Zyl-Smit RN;Zhang Y
通讯作者：
Zhang Y
DOI：
10.1084/jem.177.2.249
发表时间：
1993-02-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Carmichael A;Jin X;Sissons P;Borysiewicz L
通讯作者：
Borysiewicz L
影响因子：
7.4
作者：
Acierno, Paula M;Newton, Danforth A;Gattoni-Celli, Sebastiano
通讯作者：
Gattoni-Celli, Sebastiano
影响因子：
56.9
作者：
Altman, JD;Moss, PAH;Davis, MM
通讯作者：
Davis, MM