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

慢性活动性 Epstein-Barr 病毒病患者的淋巴细胞表现出 PD-1/PD-L1 表达升高和普遍的 Th2 免疫反应

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作者: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

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.

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.

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