体外转化调节性T细胞与同一供体未刺激细胞相比抑制活性增加

IF 0.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
V. G. Blinova, Y. A. Gladilina, D. D. Eliseeva, T. A. Lobaeva, D. D. Zhdanov
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引用次数: 0

摘要

调节性T细胞CD4+CD25+FoxP3+СD127low (Tregs)在维持对自身抗原的耐受性,抑制效应T和B淋巴细胞的功能,并在免疫的效应和调节臂之间提供平衡方面发挥关键作用。自身免疫性疾病患者的特点是Treg数量减少和抑制活性受损。体外转化的自体Tregs替代疗法可以恢复被破坏的免疫系统平衡。我们开发了一种培养Treg前体细胞的方法。使用这种方法,我们能够在一周内从50 mL的外周血中培养出3 - 4亿个Treg细胞。在这项研究中,我们证明了90 - 95%的离体转化treg具有CD4+CD25+FoxP3+СD127low表型,并且增加了FoxP3和Helios基因的转录。体外转化Tregs的特征是FoxP3启动子的去甲基化增加,增殖基因标记细胞周期蛋白B1、Ki67和LGALS 1的激活。体外转化的Tregs具有增强的抑制活性,高达80-90%的这些细胞分泌细胞因子TNFα和IFNγ。我们的数据表明体外转化的自体Tregs具有调节性T细胞的遗传、免疫表型和功能特征。在未来,它们可用于自身免疫性疾病的过继免疫治疗和移植免疫抑制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Increased Suppressor Activity of Ex Vivo Transformed Regulatory T Cells in Comparison with Unstimulated Cells of the Same Donor

Increased Suppressor Activity of Ex Vivo Transformed Regulatory T Cells in Comparison with Unstimulated Cells of the Same Donor

Abstract

Regulatory T cells CD4+CD25+FoxP3+СD127low (Tregs) play a key role in the maintenance of tolerance to autoantigens, inhibit the function of effector T and B lymphocytes, and provide a balance between effector and regulatory arms of immunity. Patients with autoimmune diseases are characterized by decreased Treg numbers and impaired suppressive activity. Replacement therapy with autologous Tregs transformed ex vivo could restore the destroyed balance of the immune system. We developed a method for the cultivation of Treg precursor cells. Using this method, we were able to grow up to 300−400 million Treg cells from 50 mL of peripheral blood during a week. In this study, we demonstrated that 90−95% of ex vivo-transformed Tregs had the phenotype CD4+CD25+FoxP3+СD127low and increased the transcription of the FoxP3 and Helios genes. Ex vivo-transformed Tregs were characterized by increased demethylation of the FoxP3 promoter and activation of the proliferation gene markers cyclin B1, Ki67 and LGALS 1. Ex vivo-transformed Tregs had increased suppressive activity, and up to 80–90% of these cells secreted the cytokines TNFα and IFNγ. Our data suggest that ex vivo-transformed autologous Tregs have genetic, immunophenotypic and functional characteristics of regulatory T cells. In the future, they can be used for adoptive immunotherapy of autoimmune diseases and inhibition of transplantation immunity.

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来源期刊
CiteScore
1.10
自引率
0.00%
发文量
31
期刊介绍: Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry   covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.
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