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首页> 外文期刊>International Immunology >Priming and stimulation of hepatitis C virus-specific CD4+ and CD8+ T cells against HCV antigens NS4, NS5a or NS5b from HCV-naive individuals: implications for prophylactic vaccine
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Priming and stimulation of hepatitis C virus-specific CD4+ and CD8+ T cells against HCV antigens NS4, NS5a or NS5b from HCV-naive individuals: implications for prophylactic vaccine

机译:丙型肝炎病毒特异性CD4 + 和CD8 + T细胞针对未感染HCV的个体的HCV抗原NS4,NS5a或NS5b的启动和刺激:对预防性疫苗的影响

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Hepatitis C virus (HCV) is a devastating human pathogen, yet there is no vaccine available for this virus. From studies with acute or chronic HCV-infected humans and chimpanzees, T-cell responses against HCV-derived conserved non-structural antigens have been correlated with viral clearance. In this study, recombinant adenoviral vectors containing HCV-derived NS4, NS5a or NS5b genes were employed to endogenously express the HCV antigens in human dendritic cells (DCs). The DCs expressing these HCV antigens exhibited normal phenotype and function. Intriguingly, we found that the DCs expressing HCV NS4, NS5a or NS5b antigens were able to significantly stimulate autologous T cells obtained from uninfected healthy individuals. These T cells produced various cytokines and proliferated in an HCV antigen-dependent manner. Evidence of both CD4+ and CD8+ T-cell responses generated in vitro against HCV NS4, NS5a or NS5b were obtained. HCV NS4 was much less stimulatory for CD4+ and CD8+ T cells than NS5. Further, in secondary assays, the CD4+ T cells primed in vitro exhibited HCV antigen-specific proliferative responses against recombinant protein antigens. In summary, we provide conclusive evidence of in vitro stimulation of CD4+ and CD8+ T cells from HCV-naive individuals against HCV antigens NS4, NS5a and NS5b. The studies with naive T cells represent early events in the induction of cellular immune responses, which most likely govern the outcome of HCV infection. These studies have significant implications in designing vaccines for HCV infection in both prophylactic and therapeutic settings.
机译:丙型肝炎病毒(HCV)是一种毁灭性的人类病原体,但目前尚无针对该病毒的疫苗。根据对急性或慢性HCV感染的人和黑猩猩的研究,针对HCV衍生的保守非结构性抗原的T细胞应答与病毒清除率相关。在这项研究中,使用包含HCV衍生的NS4,NS5a或NS5b基因的重组腺病毒载体,在人树突状细胞(DC)中内源表达HCV抗原。表达这些HCV抗原的DC表现出正常的表型和功能。有趣的是,我们发现表达HCV NS4,NS5a或NS5b抗原的DC能够显着刺激从未感染健康个体获得的自体T细胞。这些T细胞产生各种细胞因子并以HCV抗原依赖性方式增殖。获得了体外针对HCV NS4,NS5a或NS5b产生的CD4 + 和CD8 + T细胞应答的证据。 HCV NS4对CD4 + 和CD8 + T细胞的刺激作用远小于NS5。此外,在二级测定中,体外引发的CD4 + T细胞表现出针对重组蛋白抗原的HCV抗原特异性增殖反应。总而言之,我们提供了体外实验证明来自HCV初次感染者的CD4 + 和CD8 + T细胞针对HCV抗原NS4,NS5a和NS5b的确凿证据。幼稚T细胞的研究代表了诱导细胞免疫反应的早期事件,最有可能控制HCV感染的结果。这些研究对设计预防和治疗HCV感染疫苗具有重要意义。

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