Expression of programmed cell death1 in T follicular helper cells is regulated by prostaglandin E2 secreted by HBV-infected HepG2.2.1.5 cells

Sui,Zhefeng; Shi,Ying; Gao,Zhiling; Yang,Deguang; Wang,Zhihao

doi:10.3892/mmr.2017.6503

Expression of programmed cell death1 in T follicular helper cells is regulated by prostaglandin E2 secreted by HBV-infected HepG2.2.1.5 cells

Authors:
- Zhefeng Sui
- Ying Shi
- Zhiling Gao
- Deguang Yang
- Zhihao Wang
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Affiliations: Department of Nursing, Hulunbeier Vocational Technical College, Hulunbuir, Inner Mongolia 021000, P.R. China, Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Pharmacy, Baicheng Medical College, Baicheng, Jilin 137000, P.R. China, Department of Cardiology, The Third Hospital of Southern Medical University, Guangzhou, Guangdong 510000, P.R. China, Department of Gerontology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: April 24, 2017 https://doi.org/10.3892/mmr.2017.6503
Pages: 4305-4311

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Abstract

The present study aimed to investigate the distribution of T follicular helper (Tfh)-cell subsets in patients with hepatitis B virus (HBV) and determine the underlying mechanism of HBV regulation of Tfh cells. The frequency of peripheral blood Tfh subsets was analyzed using flow cytometry. The expression level of programmed cell death‑1 (PD‑1) and prostaglandin E2 (PGE2) was quantified using reverse transcription‑quantitative polymerase chain reaction and western blotting. The PGE2 level in culture supernatant was detected using enzyme‑linked immunosorbent assay. A Transwell chamber was used to co‑culture Tfh cells with HepG2 and HepG2.2.1.5. The percentage of inducible T‑cell costimulator (ICOS)+ and total Tfh cells was high at the immune activation (IA) group; however, it was reduced in the immune tolerance (IT), responders with HBsAg seroconversion (RP) and healthy control (HC) groups. The percentage of PD‑1+ Tfh cells was significantly higher in IA and IT compared with RP and HC. The ratio of PD‑1+/total Tfh cells was positively correlated with the load of HBV DNA; therefore, this ratio may act as an indicator for HBV replication. The expression level of PD‑1 in Tfh cells was higher in the HepG2.2.1.5 co‑cultured group compared with the HepG2 group, this may be due to the high PGE2 expression level in HBV‑infected HepG2.2.1.5 cells. The findings of the present study revealed an imbalanced distribution of PD‑1+ Tfh cells in patients with HBV at different immune phases. Additionally, HBV may upregulate the expression of PD‑1 in Tfh cells by promoting HepG2.2.1.5 to secret PGE2. Identifying the effect of HBV on Tfh‑cell subsets is crucial for improving immuno-based therapy for HBV.

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