CD8+Treg源性小细胞外囊泡对胶原诱导小鼠关节炎症干预作用的初步研究*

doi:10.3969/j.issn.1671-2587.2026.04.005

临床输血与检验 ›› 2026, Vol. 28 ›› Issue (4): 490-495.DOI: 10.3969/j.issn.1671-2587.2026.04.005

CD8⁺Treg源性小细胞外囊泡对胶原诱导小鼠关节炎症干预作用的初步研究^*

杨懿铭, 高跞, 蒋雪玉, 杨洁

上海市血液中心,上海 200051

收稿日期:2026-07-07 出版日期:2026-08-20 发布日期:2026-08-26
通讯作者: 杨洁,主要从事细胞治疗、血液保存等输血医学研究,（E-mail）yangjie@sbc.org.cn。
作者简介:杨懿铭,主要从事细胞治疗等输血医学研究,（E-mail）yangyiming@sbc.org.cn。
基金资助:
^*本课题受上海市血液中心科技基金项目（No.03J2102-11,L21-11）资助

Preliminary Investigation of Interventional Effects of CD8⁺ Treg-derived Small Extracellular Vesicles on Collagen-induced Arthritis in Mice

YANG Yiming, GAO Li, JIANG Xueyu, YANG Jie

Shanghai Blood Center, Shanghai 200051

Received:2026-07-07 Online:2026-08-20 Published:2026-08-26

摘要/Abstract

摘要： 目的分离人外周血诱导培养CD8⁺Treg上清来源小细胞外囊泡（sEV）,探究其过继输注对胶原诱导性关节炎（CIA）小鼠的治疗效果。方法差速结合超速离心法提取sEV,借助粒径分析、透射电镜及蛋白印迹鉴定囊泡理化特征。CIA小鼠随机分为对照组与sEV干预组,干预后进行关节炎症评分、关节组织病理学观察;检测血浆炎症因子与Ⅱ型胶原抗体水平,采用流式分析淋巴结CD4⁺T细胞亚群改变。结果所得囊泡呈典型杯状结构,平均粒径（106.8±3.3）nm,高表达CD63、TSG101标志物。相较于对照组,sEV干预组小鼠关节炎发病延缓、关节炎症与软骨破坏减轻;血浆TNF-α、IL-6及Ⅱ型胶原抗体含量显著下降,淋巴结CD4⁺IFN-γ⁺、CD4⁺IL-4⁺T细胞比例上调。结论 CD8⁺Treg来源sEV可下调模型小鼠炎性因子、调控CD4⁺T细胞分化,有效缓解CIA小鼠关节炎症。

关键词: CD4⁺T细胞亚群, 炎性因子, CD8⁺调节性T细胞, 外囊泡体, 胶原诱导关节炎

Abstract: Objective To investigate the therapeutic efficacy of adoptively transferred sEV in mice with collagen-induced arthritis (CIA), we isolated small extracellular vesicles (sEV) from the culture supernatant of human peripheral blood-derived induced CD8⁺Treg cells. Methods sEV were isolated via differential ultracentrifugation and characterized by nanoparticle tracking analysis, transmission electron microscopy and western blotting. CIA mice were randomly assigned into control and sEV-treated groups. After intervention, clinical arthritis scoring and histopathological examination of joint tissues were examined. Plasma levels of proinflammatory cytokines and anti-type II collagen antibodies were detected, and CD4⁺ T cell subsets in lymph nodes were quantified by flow cytometry. Results Purified sEV exhibited a typical cup-shaped morphology with an average diameter of 106.8±3.3 nm and expression of CD63 and TSG101. Compared with controls, the sEV-treated group displayed delayed disease onset, alleviated articular inflammation and reduced cartilage erosion. Consistently, plasma TNF-α, IL-6 and anti-type Ⅱ collagen antibodies were markedly reduced, while the frequencies of lymph node CD4⁺IFN-γ⁺ and CD4⁺IL-4⁺ T cells were elevated. Conclusion CD8⁺Treg-derived sEV alleviate joint inflammation in CIA mice by suppressing inflammatory cytokines and modulating CD4⁺ T cell differentiation.

Key words: CD4⁺ cell subsets, Inflammatory cytokine, CD8⁺ regulatory T cells, Extracellular vesicles, Collagen-induced arthritis

中图分类号:

R392.11

杨懿铭, 高跞, 蒋雪玉, 杨洁. CD8⁺Treg源性小细胞外囊泡对胶原诱导小鼠关节炎症干预作用的初步研究^*[J]. 临床输血与检验, 2026, 28(4): 490-495.

YANG Yiming, GAO Li, JIANG Xueyu, YANG Jie. Preliminary Investigation of Interventional Effects of CD8⁺ Treg-derived Small Extracellular Vesicles on Collagen-induced Arthritis in Mice[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2026, 28(4): 490-495.

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CD8⁺Treg源性小细胞外囊泡对胶原诱导小鼠关节炎症干预作用的初步研究^*

Preliminary Investigation of Interventional Effects of CD8⁺ Treg-derived Small Extracellular Vesicles on Collagen-induced Arthritis in Mice

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CD8+Treg源性小细胞外囊泡对胶原诱导小鼠关节炎症干预作用的初步研究*

Preliminary Investigation of Interventional Effects of CD8+ Treg-derived Small Extracellular Vesicles on Collagen-induced Arthritis in Mice

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CD8⁺Treg源性小细胞外囊泡对胶原诱导小鼠关节炎症干预作用的初步研究^*

Preliminary Investigation of Interventional Effects of CD8⁺ Treg-derived Small Extracellular Vesicles on Collagen-induced Arthritis in Mice