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产生 IgE 特异性细胞毒性 T 淋巴细胞作为一种新型免疫治疗方法用于治疗过敏性哮喘。

Generation of IgE-specific cytotoxic T lymphocytes as a novel immunotherapeutic approach for the treatment of allergic asthma.

机构信息

College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.

College Hospital, Zhejiang Sci-Tech University, Hangzhou, China.

出版信息

Singapore Med J. 2020 Apr;61(4):212-220. doi: 10.11622/smedj.2019068. Epub 2019 Jul 11.

Abstract

INTRODUCTION

Overproduction of immunoglobulin E (IgE) by a subset of B cells plays a key role in the pathogenesis of allergic asthma. Anti-IgE monoclonal antibodies have been successfully used to treat the disease, but long-term application is required.

METHODS

For this study, cytotoxic T lymphocytes (CTLs) against IgE-producing B cells were generated ex vivo by stimulating naive CD8 T cells with IgE-derived peptides presented by Drosophila-derived artificial antigen-presenting cells. Based on the treatment of allergic asthma in mice, the inhibitive effect of this CTL on IgE responses and airway inflammation was determined with the enzyme-linked immunosorbent assay and histochemical method.

RESULTS

The IgE-specific CTLs effectively lysed target cells in vitro, while the adoptively transferred CTLs specifically inhibited IgE responses and airway inflammation in an asthmatic mouse model. The effect of IgE-specific CTLs is MHC (major histocompatibility complex) Class I-restricted and requires the expression of perforin.

CONCLUSION

IgE-specific CTLs generated ex vivo may provide a novel treatment for allergic asthma and lead to a new therapy for other immunological disorders.

摘要

简介

B 细胞亚群产生的免疫球蛋白 E(IgE)过多在过敏性哮喘的发病机制中起关键作用。抗 IgE 单克隆抗体已成功用于治疗该疾病,但需要长期应用。

方法

为了进行这项研究,通过用果蝇衍生的人工抗原呈递细胞呈递的 IgE 衍生肽刺激幼稚 CD8 T 细胞,在体外产生针对 IgE 产生 B 细胞的细胞毒性 T 淋巴细胞(CTL)。基于对小鼠过敏性哮喘的治疗,通过酶联免疫吸附试验和组织化学方法确定该 CTL 对 IgE 反应和气道炎症的抑制作用。

结果

IgE 特异性 CTL 在体外有效裂解靶细胞,而过继转移的 CTL 特异性抑制哮喘小鼠模型中的 IgE 反应和气道炎症。IgE 特异性 CTL 的作用受 MHC(主要组织相容性复合体)I 类限制,需要穿孔素的表达。

结论

体外产生的 IgE 特异性 CTL 可能为过敏性哮喘提供一种新的治疗方法,并为其他免疫性疾病带来新的治疗选择。

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