Inflammation and Infection Research Centre, School of Medical Sciences, Sydney, NSW, Australia.
J Viral Hepat. 2013 Apr;20(4):e96-106. doi: 10.1111/jvh.12016. Epub 2012 Oct 15.
Some hepatitis C (HCV)-uninfected, high-risk individuals have HCV-specific cellular immunity without viraemia or seroconversion. The characteristics of these responses and the risk behavioural associations were studied in 94 subjects in a prospective cohort of recently seronegative prisoners reporting injecting drug use (IDU). Detailed behavioural data were collected. HCV antibody and PCR testing were performed. ELISpot assays for HCV-induced interferon (IFN)-γ and interleukin (IL)-2 production by T lymphocytes, as well as multiplex in vitro cytokine production assays, were performed. Seventy-eight subjects remained antibody and PCR negative and 16 seroconverted. Of the seronegative group, 22 (28%) had IFN-γ ELISpot responses in comparison with 13 of the 16 seroconverters (82%). This seronegative immune status was associated positively with injecting anabolic steroids and negatively with a recent break from IDU. The IFN-γ ELISpot responses involved both CD4 and CD8 T lymphocytes and were comparable in magnitude, but narrower in specificity, in uninfected subjects than in seroconverters. A subset of seronegative subjects had HCV-induced cytokine production patterns comparable with the seroconverters with increased production of IFN-γ, IL-2 and tumour necrosis factor (TNF)-α and reduced IL-10 in response to nonstructural peptides. In conclusion, comparable patterns of HCV-specific cellular immunity are found in recently infected subjects and in a minority of high-risk, uninfected subjects. Further characterization of these responses and their protective efficacy will inform HCV vaccine development.
一些未感染丙型肝炎病毒（HCV）的高危个体具有针对 HCV 的细胞免疫应答，而无病毒血症或血清转换。本研究在最近血清学阴性的报告静脉注射吸毒（IDU）的囚犯前瞻性队列中 94 例受试者中研究了这些应答的特征和风险行为关联。收集了详细的行为数据。进行了 HCV 抗体和 PCR 检测。进行了 T 淋巴细胞产生 HCV 诱导的干扰素（IFN）-γ和白细胞介素（IL）-2的 ELISpot 检测，以及体外细胞因子产生的多重分析。78 例受试者的抗体和 PCR 仍为阴性，16 例发生血清转换。在血清阴性组中，22 例（28%）与 16 例血清转换者（82%）相比有 IFN-γ ELISpot 反应。这种血清阴性免疫状态与注射合成代谢类固醇呈正相关，与最近停止 IDU 呈负相关。IFN-γ ELISpot 反应涉及 CD4 和 CD8 T 淋巴细胞，在未感染者中的数量和特异性与血清转换者相当，但更窄。一部分血清阴性受试者具有与血清转换者相似的 HCV 诱导的细胞因子产生模式，对非结构肽的反应中 IFN-γ、IL-2 和肿瘤坏死因子（TNF）-α的产生增加，IL-10 减少。总之，在近期感染的受试者和少数高危、未感染者中发现了类似的 HCV 特异性细胞免疫模式。进一步对这些应答及其保护效果进行表征将有助于 HCV 疫苗的开发。
