系统性红斑狼疮与类风湿性关节炎患者外周负性共刺激分子PD-1与调节性T淋巴细胞免疫紊乱的研究
Research on the disturbance of negative costimulator PD-1 and regulatory T cells in patients with systemic lupus erythematosus and rheumatoid arthritis
目的:从细胞免疫调控角度,结合负性共刺激分子PD-1在各类T细胞亚群的分布进行分析,探讨SLE和RA患者外周调节性T细胞与效应性T细胞平衡状态,了解PD-1分子对各类T细胞亚群调控效应。材料与方法:我院确诊的SLE患者40例,类风湿性关节炎患者50例及健康志愿者19例。采用流式细胞术分析SLE、RA患者及健康对照者外周T淋巴细胞亚群及CD4+CD25high Treg细胞和CD4+CD25low Teff细胞表达率,负性刺激分子PD-1在各淋巴细胞亚群表面的表达率。结果: ⑴ 与健康对照组相比,SLE患者外周以CD3+CD8+T细胞高表达为特征(P<0.05);RA患者外周以CD3+CD4+T细胞高表达率和CD4/CD8高比值为特征(P<0.05)。⑵ 与健康对照组比较,SLE和RA患者外周CD4+CD25high Treg细胞和CD4+CD25low Teff细胞均降低,但仅Treg细胞表达率显著降低(P<0.05),Teff/Treg比值显著增加。⑶ SLE和RA患者外周CD3+T细胞、CD3+CD4+T细胞和CD3+CD8+T细胞表面PD-1分子表达率均较健康对照组显著增加(P<0.05),且SLE患者PD-1分子表达率明显高于RA患者(P<0.05)。⑷ RA患者Teff细胞和Treg细胞表面PD-1分子表达率最低(与健康对照组和SLE患者比较,P均<0.05),SLE患者表达率最高,但与健康对照组无显著差异。结论:SLE和RA患者外周T淋巴细胞表面PD-1分子在功能上并未发挥有效免疫抑制效应。低表达的外周Treg细胞是介导SLE患者免疫耐受紊乱的主要因素;低表达的CD4+CD25+Treg细胞及其表面低表达PD-1分子的共同作用是介导RA患者免疫抑制效应不足的重要因素之一。
Objectives: To explore the balance state of peripheral regulatory T cells and effector T cells, as well as preliminarily learn the regulatory role of programmed death-1 (PD-1) on different T cell subsets in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods: 40 patients with SLE, 50 patients with RA and 19 healthy volunteers were included. Peripheral T cells subsets, CD4+CD25high regulatory T cells (Treg) and CD4+CD25low effector T cells (Teff), as well as the percentage of PD-1 on different lymphocyte subsets were all detected by flow cytometry. Results: ⑴ Compared with healthy control (HC), high percentage of peripheral CD3+CD8+T cells was the characteristics of SLE, and high percentage of CD3+CD4+T cells and high CD4/CD8 ratio were the features of RA. ⑵ Percentage of peripheral CD4+CD25high Treg cells and CD4+CD25low Teff cells in SLE and RA was lower than those in HC (only Treg cells significantly decreased, P<0.05),Teff/Treg ratio strikingly increased compared with HC。⑶ Compared with HC, the percentage of PD-1 on CD3+T cells, CD3+CD4+T cells and CD3+CD8+T cells was all significantly increased in SLE and RA, and that in SLE was strikingly higher than that in RA(P<0.05).⑷ The percentage of PD-1 on peripheral Treg cells or Teff cells was the lowest in RA (compared with HC or SLE, all P<0.05), and was highest in SLE (compared with HC, P>0.05) . conclusions:Negative costimulator PD-1 couldn't play an important role in immune suppression in SLE or RA patients. Low percentage of Treg cells was the critical factor in the disturbed immune in SLE; and the synergistic effects of low expression PD-1 on CD4+CD25+Treg cells and decreased Treg cells was one of important factors to cause the insufficient immune suppression in RA.
牛倩、王兰兰、蔡蓓、罗俐梅、黄卓春、冯伟华
基础医学内科学
系统性红斑狼疮/SLE类风湿性关节炎/RA程序性死亡分子-1/PD-1调节性T淋巴细胞
systemic lupus erythematosus/SLErheumatoid arthritis/RAprogrammed death-1/PD-1regulatory T cells
牛倩,王兰兰,蔡蓓,罗俐梅,黄卓春,冯伟华.系统性红斑狼疮与类风湿性关节炎患者外周负性共刺激分子PD-1与调节性T淋巴细胞免疫紊乱的研究[EB/OL].(2013-02-27)[2025-08-11].http://www.paper.edu.cn/releasepaper/content/201302-473.点此复制
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