Yang Yuhang, Liu Kanghao, Zhou Wenwen, Dai Shenglan
Department of Gastroenterology, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
Exp Ther Med. 2023 Feb 28;25(4):167. doi: 10.3892/etm.2023.11866. eCollection 2023 Apr.
Hepatitis B virus (HBV) infection is a major public health concern. The clearance of HBV may involve cytotoxic T-lymphocyte (CTL) activity and T helper type 1 reactions. Exosomes generated from dendritic cells (DCs) can induce immunological responses capable of eradicating viruses. However, exosomes loaded with antigens have not yet demonstrated therapeutic potential in HBV infection. Therefore, the present study aimed to investigate the antiviral effects of DC-derived exosomes (Dexs) loaded with ubiquitinated HBV core antigen (Dexs-Ub-HBcAg). Murine bone marrow-derived DCs were loaded with a recombinant lentivector encoding the ubiquitinated form of HBcAg. High-purity Dexs were generated using differential velocity centrifugation. Splenic T-lymphocytes were stimulated with Dexs-Ub-HBcAg and the specific T-cell-mediated immune responses were examined. Cytokine expression was analyzed using enzyme-linked immunosorbent assays. T-lymphocyte proliferation was detected using a Cell Counting Kit-8 assay and HBcAg-specific CTL activity was determined using a lactate dehydrogenase release assay. The results revealed that Dexs-Ub-HBcAg effectively stimulated T-cell proliferation and induced the activation of antigen-specific CTLs to exhibit HBcAg-specific CTL immune responses . These results suggest the potential of Dexs-Ub-HBcAg for development as a future therapeutic option for the elimination of HBV.
乙型肝炎病毒(HBV)感染是一个重大的公共卫生问题。HBV的清除可能涉及细胞毒性T淋巴细胞(CTL)活性和1型辅助性T细胞反应。树突状细胞(DC)产生的外泌体可诱导能够根除病毒的免疫反应。然而,负载抗原的外泌体在HBV感染中尚未显示出治疗潜力。因此,本研究旨在探讨负载泛素化HBV核心抗原的DC来源外泌体(Dexs-Ub-HBcAg)的抗病毒作用。用编码泛素化形式HBcAg的重组慢病毒载体负载小鼠骨髓来源的DC。使用差速离心法产生高纯度的Dexs。用Dexs-Ub-HBcAg刺激脾T淋巴细胞,并检测特异性T细胞介导的免疫反应。使用酶联免疫吸附测定法分析细胞因子表达。使用细胞计数试剂盒-8测定法检测T淋巴细胞增殖,并使用乳酸脱氢酶释放测定法测定HBcAg特异性CTL活性。结果显示,Dexs-Ub-HBcAg有效刺激T细胞增殖并诱导抗原特异性CTL活化,以表现出HBcAg特异性CTL免疫反应。这些结果表明Dexs-Ub-HBcAg作为未来消除HBV的治疗选择具有开发潜力。