Hepatitis B e antigen from chronic hepatitis B patients induces Th1/Th2 cytokine imbalance in vitro.
- VernacularTitle:HBeAg导致慢性乙型肝炎患者外周血Th1/Th2型细胞因子失衡
- Author:
Ya-ping HAN
1
;
Jun LI
;
Long-feng JIANG
;
Qing-qing XU
;
Bo LIU
;
Li DONG
;
Nian CHEN
;
Lian-hua KONG
;
Fa-ren XIE
;
Zu-hu HUANG
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Case-Control Studies; Cells, Cultured; Female; Hepatitis B e Antigens; genetics; immunology; Hepatitis B, Chronic; blood; immunology; Humans; Interferon-gamma; immunology; Interleukin-10; immunology; Interleukin-6; immunology; Leukocytes, Mononuclear; immunology; metabolism; Male; Middle Aged; Recombinant Proteins; immunology; Th1 Cells; immunology; Th1-Th2 Balance; Th2 Cells; immunology
- From: Chinese Journal of Hepatology 2013;21(8):584-589
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the immunoregulatory effect of hepatitis B virus (HBV) e antigen (HBeAg) on peripheral blood monocytes (PBMCs).
METHODSPBMCs were isolated from patients with chronic hepatitis B (CHB; both HBeAg- and HBeAg+) and healthy controls, and cultured with recombinant HBeAg. The HBeAg-induced changes in expression of PD-1/PD-L1 were measured by flow cytometry of the cells and in secreted cytokines were measured by enzyme-linked immunosorbent assay of the supernatants. Comparisons between two groups were made by the independent-samples t-test; the relationship between PD-1/B7-H1 level and HBV DNA copy number was evaluated by Spearman's correlation analysis.
RESULTSExposure to HBeAg led to a significant decrease in CD3+CD4+ T lymphocyte-specific expression of IFNa for both the CHB patients' and healthy controls' samples (t = 2.382 and -4.190 respectively, P less than 0.01). For the HBeAg- CHB patients' and healthy controls' samples, the HBeAg exposure led to increased levels of secreted cytokines IL-6, IL-10 and TNFa (t = 2.504, 3.583 and 4.324, P less than 0.01 and t = 3.542, 6.246 and 5.273, P less than 0.01 respectively) and of CD14+ PBMC-specific expression of PD-L1 (t = 4.815 and 3.454, P less than 0.05 respectively). Compared to the HBeAg-negative CHB patients' and healthy controls' samples, the HBeAg+ CHB patients' samples had significantly lower CD3+CD4+ T cell-specific expression of IFNa (t = -3.177 and -4.541, P less than 0.01 respectively), but significantly higher levels of secreted IL-4 (t = 3.382 and 4.393, P less than 0.01 respectively), of CD3+ T cells-specific expression of PD-1/PD-L1 (t = 4.755, 2.942 and 4.518, 4.595, P less than 0.01 respectively), and of CD14+ T cells-specific expression of PD-L1 (t = 5.092 and 5.473, P less than 0.01 respectively). The CD3+ T cells-specific expression of PD-L1 was significantly higher in the samples from HBeAg- CHB patients than from the healthy controls (t = 3.214, P less than 0.01).
CONCLUSIONHBeAg was able to down-regulate the production of Th1-type cytokines (IFNgamma), and up-regulate the secretion of Th2-type cytokines (IL-6, IL-10) and the expression of PD-1/PD-L1on monocytes. These changes are conducive to the formation of immune tolerance to HBV. Therefore, HBeAg may play an important role in immune tolerance to chronic HBV infection.