Development of CD8+ T cells expressing two distinct receptors specific for MTB and HIV-1 peptides
Development of CD8+ T cells expressing two distinct receptors specific for MTB and HIV-1 peptides
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开发表达 MTB 和 HIV-1 肽特异性的两种不同受体的 CD8 T 细胞
DOI：
10.1111/jcmm.12053
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发表时间：
2013-04-04
影响因子：
5.3
通讯作者：
Ma L
中科院分区：
文献类型：
--
作者：
Hao PP;Zhang XB;Luo W;Zhou CY;Wen Q;Yang Z;Liu SD;Jiang ZM;Zhou MQ;Jin Q;Ma L
结核分枝杆菌（MTB）和人类免疫缺陷病毒（MTB/HIV）共同感染的个体的免疫应答逐渐恶化，特别是在细胞区室中。功能性效应T细胞的连续转移可以赋予免疫缺陷MTB/HIV共感染受体保护性免疫。然而，体内几乎不存在这样的效应T细胞，并且它们的分离和扩增到足够的数量是困难的。因此，增强针对两种病原体的免疫应答对于治疗MTB/HIV共感染患者至关重要。一种方法是过继转移T细胞受体（TCR）基因修饰的T细胞用于治疗MTB/HIV共感染，因为TCR基因转移显著增加了淋巴细胞数量及其功能性亲合力。为了产生双特异性CD 8 + T细胞，分离MTB Ag 85 B199 -207肽特异性TCR（MTB/TCR）和HIV-1 Env 120 -128肽特异性TCR（HIV/TCR），并使用逆转录病毒载体同时引入CD 8 + T细胞。为了避免外源性和内源性TCR之间的错配，并提高引入的TCR的功能和稳定性，采用了几种策略，包括在MTB/TCR恒定（C）区中引入突变，用CD 3 γ取代HIV/TCR C区的一部分，以及用三种不同的2A肽连接基因片段。本报告中提出的结果表明，工程化的T细胞具有肽特异性的特异性，导致细胞因子的产生和细胞毒活性。这是第一份描述产生特异性针对两种不同病原体的工程化T细胞的报告，并为治疗免疫功能低下的MTB/HIV共感染患者的TCR基因治疗提供了新的见解。
The immune response in individuals co-infected with Mycobacterium tuberculosis (MTB) and the human immunodeficiency virus (MTB/HIV) gradually deteriorates, particularly in the cellular compartment. Adoptive transfer of functional effector T cells can confer protective immunity to immunodeficient MTB/HIV co-infected recipients. However, few such effector T cells exist in vivo, and their isolation and amplification to sufficient numbers is difficult. Therefore, enhancing immune responses against both pathogens is critical for treating MTB/HIV co-infected patients. One approach is adoptive transfer of T cell receptor (TCR) gene-modified T cells for the treatment of MTB/HIV co-infections because lymphocyte numbers and their functional avidity is significantly increased by TCR gene transfer. To generate bispecific CD8+ T cells, MTB Ag85B199–207 peptide-specific TCRs (MTB/TCR) and HIV-1 Env120–128 peptide-specific TCRs (HIV/TCR) were isolated and introduced into CD8+ T cells simultaneously using a retroviral vector. To avoid mispairing among exogenous and endogenous TCRs, and to improve the function and stability of the introduced TCRs, several strategies were employed, including introducing mutations in the MTB/TCR constant (C) regions, substituting part of the HIV/TCR C regions with CD3ζ, and linking gene segments with three different 2A peptides. Results presented in this report suggest that the engineered T cells possessed peptide-specific specificity resulting in cytokine production and cytotoxic activity. This is the first report describing the generation of engineered T cells specific for two different pathogens and provides new insights into TCR gene therapy for the treatment of immunocompromised MTB/HIV co-infected patients.
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影响因子：
4.2
作者：
Lopez-Alvarez R;Badillo-Lopez C;Cerna-Cortes JF;Castillo-Ramirez I;Rivera-Gutierrez S;Helguera-Repetto AC;Aguilar D;Hernandez-Pando R;Samper S;Gonzalez-y-Merchand JA
通讯作者：
Gonzalez-y-Merchand JA
影响因子：
3.7
作者：
Georghiou SB;Magana M;Garfein RS;Catanzaro DG;Catanzaro A;Rodwell TC
通讯作者：
Rodwell TC
影响因子：
2.6
作者：
Gottschalk, S;Heslop, HE;Rooney, CM
通讯作者：
Rooney, CM
影响因子：
5.4
作者：
Feeney, ME;Tang, Y;Goulder, PJR
通讯作者：
Goulder, PJR
DOI：
10.1016/j.bbrc.2010.02.141
发表时间：
2010-05-21
影响因子：
3.1
作者：
Brighenti, Susanna;Andersson, Jan
通讯作者：
Andersson, Jan