Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Cell Immunol. 2013 May-Jun;283(1-2):25-30. doi: 10.1016/j.cellimm.2013.05.009. Epub 2013 Jun 12.
This study is to observe the expression of B7-H1, PD-1 and TLR2 on peripheral blood monocytes (PBMCs) regulated by HBeAg in chronic hepatitis B (CHB), and to illustrate the relation between HBeAg and persistent infection of HBV. In both CHB patients and healthy controls, the expression of B7-H7 was significantly increased on CD14(+) monocytes incubated with HBeAg, while that of TLR2 was significantly reduced; the expression of specific IFN-γ was significantly decreased in CD3(+)CD4(+) T lymphocytes incubated with HBeAg, while IL-6 and IL-10 in conditioned media were significantly increased. HBeAg is able to significantly up-regulate B7-H1, down-regulate TLR2 on monocytes, reduce IFN-γ produced by T lymphocytes and increase Th2-type cytokines secretion. These findings suggest that HBeAg suppresses the specific cellular immunity to clear the virus, and eventually lead to immune tolerance to HBV infection. Therefore, HBeAg plays an important role in immune suppression in chronic HBV patients.
本研究旨在观察乙型肝炎病毒 e 抗原(HBeAg)调控慢性乙型肝炎(CHB)患者外周血单个核细胞(PBMCs)中 B7-H1、PD-1 和 TLR2 的表达,阐明 HBeAg 与 HBV 持续感染之间的关系。在 CHB 患者和健康对照者中,与未孵育 HBeAg 的 CD14(+)单核细胞相比,孵育 HBeAg 可显著上调 CD14(+)单核细胞上 B7-H7 的表达,同时显著下调 TLR2 的表达;孵育 HBeAg 可显著降低 CD3(+)CD4(+)T 淋巴细胞产生 IFN-γ的水平,而条件培养基中 IL-6 和 IL-10 的分泌显著增加。HBeAg 可显著上调单核细胞上的 B7-H1、下调 TLR2,减少 T 淋巴细胞产生 IFN-γ,增加 Th2 型细胞因子的分泌。这些发现提示 HBeAg 抑制了针对病毒的特异性细胞免疫,最终导致对 HBV 感染的免疫耐受。因此,HBeAg 在慢性乙型肝炎患者的免疫抑制中发挥重要作用。