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| 髓源性抑制细胞在长期抗HBV治疗患者中促进HBsAg阴转的作用和机制探讨 |
| Role and mechanism of myeloid-derived suppressor cells in promoting HBsAg seroclearance in patients after long-term anti-HBV treatment |
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| DOI：10.3969/j.issn.1007-8134.2019.05.005 |
| 中文关键词: 慢性乙型肝炎 乙型肝炎病毒表面抗原 髓源性抑制细胞 P47phox |
| 英文关键词: chronic hepatitis B HBsAg MDSCs P47phox |
| 基金项目:“十三五”国家科技重大专项（2017ZX10202203-0080-006） |
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| 中文摘要: |
| 目的 研究髓源性抑制细胞（myeloid-derived suppressor cells, MDSCs）、CD4+ T细胞、CD8+ T细胞、P47phox在抗病毒治疗后获得HBsAg清除及未获得HBsAg清除的2种人群外周血中的频率和表达情况，探讨MDSCs在肝炎慢性化及HBsAg清除中的作用及机制。方法 筛选2007年7月—2008年7月慢性乙型肝炎（chronic hepatitis B, CHB）患者80例予以抗HBV药物[恩替卡韦（博路定）]治疗。采用流式细胞术检测治疗前CHB组中12例及14例健康对照者外周血MDSCs、CD4+ T细胞、CD8+ T细胞占外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）总数的比例（即MDSCs、CD4+ T细胞、CD8+ T细胞频率）。追踪CHB组患者，排除治疗过程中死亡、失访等患者，72例患者成功随访8年。检测抗病毒治疗8年后8例HBsAg转阴[HBsAg（-）组]与64例未转阴[HBsAg（+）组]患者PBMCs中MDSCs、CD4+ T细胞、CD8+ T细胞频率，用Western blot技术检测P47phox蛋白的表达。结果 治疗前CHB患者PBMCs中MDSCs频率显著高于健康对照者（P＜0.05），而PBMCs中CD4+ T细胞、CD8+ T细胞频率与健康对照者无显著差异（P均＞0.05）。抗病毒治疗后CHB患者中HBsAg（-）组PBMCs中MDSCs频率低于HBsAg（+）组，CD4+ T细胞及CD8+ T细胞频率显著高于HBsAg（+）组（P均＜0.05）。抗病毒治疗后HBsAg（+）组外周血中P47phox蛋白表达显著高于HBsAg（-）组（P＜0.05）。结论 CHB患者对T细胞耐受可能与MDSCs抑制T细胞应答有关。MDSCs可能通过活性氧途径发挥免疫抑制功能，减少HBsAg清除。 |
| 英文摘要: |
| Objective To study the frequency and expression of myeloid-derived suppressor cells (MDSCs), CD4+ T cells, CD8+ T cells and P47phox in peripheral blood of patients who obtained HBsAg seroclearance and failed to obtain HBsAg seroclearance after antiviral treatment, and investigate the role and mechanism of MDSCs in chronic hepatitis B and HBsAg clearance. Methods Eighty patients with chronic hepatitis B (CHB) were screened for receiving the treatment of anti-HBV agents [entecavir (baraclude)] from July 2007 to July 2008. The ratio of MDSCs, CD4+ T cells and CD8+ T cells in peripheral blood mononuclear cells (PBMCs) of 12 CHB patients before treatment and 14 healthy control subjects was measured by flow cytometry, as the frequency of MDSCs, CD4+ T cells and CD8+ T cells. The patients in the CHB group were traced and 72 patients were followed up for 8 years after the death and lost cases during treatment were excluded. The frequency of MDSCs, CD4+ T cells and CD8+ T cells in PBMCs of 8 patients with HBsAg seroclearance [HBsAg(-) group] and 64 patients without HBsAg seroclearance [HBsAg(+) group] after 8-year antiviral treatment was measured. Western blot testing was employed to detect P47phox protein expression. Results The frequency of MDSCs in PBMCs of CHB patients before treatment was significantly higher than that of healthy control subjects (P＜0.05). There was no significant difference in the frequency of CD4+ T cells and CD8+ T cells in PBMCs between CHB patients before treatment and healthy control subjects (P＞0.05). The frequency of MDSCs in PBMCs of HBsAg(-) patients with CHB was lower than that of HBsAg(+) patients after antiviral treatment, while the frequency of CD4+ T cells and CD8+ T cells in PBMCs of HBsAg(-) patients with CHB was significantly higher than that of HBsAg(+) patients (P＜0.05). The expression of P47phox protein in peripheral blood of HBsAg(+) group was significantly higher than that of HBsAg(-) group after antiviral treatment (P＜0.05). Conclusions T cell tolerance in CHB patients may be associated with the inhibition of T cell responses by MDSCs. MDSCs may play an immunosuppressive role through the ROS pathway and reduce HBsAg clearance. |
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