Lymphocytes in Patients with Chronic Active Epstein-Barr Virus Disease Exhibited Elevated PD-1/PD-L1 Expression and a Prevailing Th2 Immune Response.

IF 2 4区 医学 Q3 HEMATOLOGY
Kang Sun, Chaofan Wu, Qi Kong, Junxia Hu, Lin Shi, Yubo Pi, Dina Suolitiken, Tingting Cui, Leilei Chen, Xiaodan He, Zhengyang Song, Lin Wu, Jingshi Wang, Zhao Wang
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引用次数: 0

Abstract

Background and objectives: Chronic active Epstein-Barr virus disease (CAEBV) is a proliferative disease of EBV+ T or natural killer (NK) cells with an unclear pathogenesis. This study aimed to examine the frequency and exhaustion levels of lymphocyte subsets in patients with CAEBV to further investigate the pathogenesis.

Methods: Using flow cytometry, we detected the frequency, expression levels of programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1), and EBV infection status of peripheral T subsets and NK cells in patients with CAEBV and healthy individuals.

Results: 24 patients and 15 healthy individuals were enrolled in this study. Patients showed notably higher expression levels of PD-1 and PD-L1 in peripheral T subsets and NK cells compared to healthy individuals (P < 0.05). EBV+ lymphocytes exhibited significantly higher PD-L1 expression levels than EBV- lymphocytes. Additionally, the frequency of effector memory T (Tem) cells was significantly increased in patients, and the PD-L1 expression level was positively correlated with the EBV load. Besides, helper T cell 2 (Th2) immune bias, also favoring EBV amplification, was found in patients, including increased Th2 cell frequency, enhanced response capacity, and elevated serum levels of associated cytokines. The distribution and PD-1 expression levels of peripheral T subsets returned to normal in patients who responded to PD-1 blockade therapy.

Conclusions: The up-regulation of the PD-1/PD-L1 pathway of peripheral T and NK cells and Th2 immune predominance jointly promoted EBV replication and the development of CAEBV. PD-1 blockade therapy reduced the PD-1 expression level of lymphocytes and helped normalize the distribution of the T subsets.

慢性活动性爱泼斯坦-巴氏病毒病患者的淋巴细胞表现出较高的 PD-1/PD-L1 表达和较强的 Th2 免疫反应。
背景和目的:慢性活动性爱泼斯坦-巴氏病毒病(CAEBV)是一种EBV+ T或自然杀伤(NK)细胞增殖性疾病,发病机制尚不清楚。本研究旨在检测 CAEBV 患者淋巴细胞亚群的频率和衰竭水平,以进一步研究其发病机制:我们使用流式细胞术检测了 CAEBV 患者和健康人外周 T 亚群和 NK 细胞的频率、程序性细胞死亡 1(PD-1)和程序性死亡配体 1(PD-L1)的表达水平以及 EBV 感染状态。与健康人相比,患者外周 T 亚群和 NK 细胞中 PD-1 和 PD-L1 的表达水平明显更高(P < 0.05)。EBV+淋巴细胞的PD-L1表达水平明显高于EBV-淋巴细胞。此外,患者的效应记忆T(Tem)细胞频率明显增加,PD-L1表达水平与EBV载量呈正相关。此外,在患者中还发现了辅助 T 细胞 2(Th2)免疫偏倚,也有利于 EBV 扩增,包括 Th2 细胞频率增加、反应能力增强以及血清中相关细胞因子水平升高。对PD-1阻断疗法有反应的患者外周T亚群的分布和PD-1表达水平恢复正常:结论:外周T细胞和NK细胞PD-1/PD-L1通路的上调以及Th2免疫优势共同促进了EB病毒的复制和CAEBV的发展。PD-1阻断疗法降低了淋巴细胞的PD-1表达水平,有助于使T亚群的分布趋于正常。
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来源期刊
CiteScore
4.20
自引率
6.20%
发文量
113
审稿时长
12 weeks
期刊介绍: Reciprocal interdependence between infectious and hematologic diseases (malignant and non-malignant) is well known. This relationship is particularly evident in Mediterranean countries. Parasitosis as Malaria, Leishmaniosis, B Hookworms, Teniasis, very common in the southeast Mediterranean area, infect about a billion people and manifest prevalently with anemia so that they are usually diagnosed mostly by experienced hematologist on blood or bone marrow smear. On the other hand, infections are also a significant problem in patients affected by hematological malignancies. The blood is the primary vector of HIV infection, which otherwise manifest with symptoms related to a reduction in T lymphocytes. In turn, infections can favor the insurgency of hematological malignancies. The causative relationship between Epstein-Barr virus infection, Helicobacter pylori, hepatitis C virus, HIV and lymphoproliferative diseases is well known.
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