PD-1/PD-L1信号轴对系统性红斑狼疮患者外周血CD19+B细胞和CD4+T细胞相互作用的影响。

IF 2 4区 医学 Q3 RHEUMATOLOGY
Zhuobei Xie, Li Dai, Haohua He, Dengxiao Hong, Honghui Tang, Wenyan Xu, Zhongxin Chen, Hongtao Wang, Baiqing Li, Changhao Xie, Yuanyuan Wang
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引用次数: 0

摘要

背景:B细胞自身耐受性缺陷和自身反应性B细胞介导的T细胞持续抗原呈递在系统性红斑狼疮(SLE)的发生和发展中起着关键作用。PD-1/PD-L1信号轴在激活后负调控TCs的免疫反应并维持免疫耐受。然而,PD-1/PD-L1信号轴对SLE患者外周血CD19+B/CD4+TCs相互作用的影响尚未得到详细研究。方法:采用流式细胞术检测50例SLE患者和41例健康对照者外周血(PB)中PD-1/PD-L1和Ki-67水平,并进一步分析PD-1+/-细胞和PD-L1+/-细胞Ki-67的表达。分离CD19+B/CD4+TCs进行细胞培养,并收集上清液以测定TC的增殖和分化。结果:SLE患者CD19+B/CD4+TCs的PD-1、PD-L1和Ki-67水平均高于HCs。SLE患者CD19+B/CD4+TCs中,PD-L1+细胞的增殖活性高于PD-L1细胞,PD-1+细胞的增殖活力高于PD-1细胞。在共培养HCs/SLE患者CD19+B/CD4+TCs的系统中,活化的BCs促进了TCs的增殖和TCs中PD-L1的表达。在共培养体系中加入抗PD-L1可以恢复TCs的增殖,并抑制IL-10/IFN-γ水平。结论:SLE患者外周血淋巴细胞CD19+B/CD4+TCs的PD-1/PD-L1轴异常,细胞增殖异常。在SLE患者的CD19+B/CD4+TCs中,PD-L1+和PD-1+细胞的增殖活性分别与SLE患者的PD-L1-和PD-1-细胞相比。SLE患者CD19+B/CD4+TCs可通过PD-1/PD-L1相互作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The effect of PD-1/PD-L1 signaling axis on the interaction between CD19+B cells and CD4+T cells in peripheral blood of patients with systemic lupus erythematosus.

Background: The defect of B cell self-tolerance and the continuous antigen presentation by T cells (TCs) mediated by autoreactive B cells (BCs) play a key role in the occurrence and development of systemic lupus erythematosus (SLE). PD-1/PD-L1 signaling axis negatively regulates the immune response of TCs after activation and maintains immune tolerance. However, the effect of PD-1/PD-L1 signaling axis on the interaction between CD19+B/CD4+TCs in the peripheral blood of patients with SLE has not been studied in detail.

Methods: PD-1/PD-L1 and Ki-67 levels in peripheral blood (PB) of 50 SLE patients and 41 healthy controls (HCs) were detected through flow cytometry, and then the expression of PD-1+/-cells and PD-L1+/-cells Ki-67 was further analyzed. CD19+B/CD4+TCs were separated for cell culture and the supernatant was collected to determine proliferation and differentiation of TCs. IL-10 and IFN-γ secretion in the supernatant was also determined using ELISA.

Results: The PD-1, PD-L1, and Ki-67 levels on CD19+B/CD4+TCs in patients with SLE were higher than HCs. In CD19+B/CD4+TCs of SLE patients, the proliferative activity of PD-L1+ cells was higher than that of PD-L1- cells, and the proliferative activity of PD-1+ cells was higher than that of PD-1- cells. In the system co-culturing CD19+B/CD4+TCs from HCs/SLE patients, activated BCs promoted TCs proliferation and PD-L1 expression among TCs. Addition of anti-PD-L1 to co-culture system restored the proliferation of TCs, and inhibited IL-10/IFN-γ level. The addition of anti-PD-L1 to co-culture system also restored Tfh and downregulated Treg in HCs.

Conclusions: Axis of PD-1/PD-L1 on CD19+B/CD4+TCs in PB of SLE patients is abnormal, and cell proliferation is abnormal. In CD19+B/CD4+TCs of SLE patients, the proliferative activity of PD-L1+ and PD-1+ cells compared with PD-L1- and PD-1- cells in SLE patients, respectively. CD19+B/CD4+TCs in SLE patients can interact through PD-1/PD-L1.

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来源期刊
Advances in Rheumatology
Advances in Rheumatology Medicine-Rheumatology
CiteScore
4.00
自引率
4.30%
发文量
41
审稿时长
53 weeks
期刊介绍: Formerly named Revista Brasileira de Reumatologia, the journal is celebrating its 60th year of publication. Advances in Rheumatology is an international, open access journal publishing pre-clinical, translational and clinical studies on all aspects of paediatric and adult rheumatic diseases, including degenerative, inflammatory and autoimmune conditions. The journal is the official publication of the Brazilian Society of Rheumatology and welcomes original research (including systematic reviews and meta-analyses), literature reviews, guidelines and letters arising from published material.
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