College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.
College Hospital, Zhejiang Sci-Tech University, Hangzhou, China.
Singapore Med J. 2020 Apr;61(4):212-220. doi: 10.11622/smedj.2019068. Epub 2019 Jul 11.
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.
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.
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.
IgE-specific CTLs generated ex vivo may provide a novel treatment for allergic asthma and lead to a new therapy for other immunological disorders.
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。
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。
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。
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。
