Sarobe Pablo, Lasarte Juan José, Casares Noelia, López-Díaz de Cerio Ascensión, Baixeras Elena, Labarga Pablo, García Nicolás, Borrás-Cuesta Francisco, Prieto Jesús
Department of Internal Medicine, Medical School and University Clinic, University of Navarra, 31008 Pamplona, Spain.
J Virol. 2002 May;76(10):5062-70. doi: 10.1128/jvi.76.10.5062-5070.2002.
Patients infected with hepatitis C virus (HCV) have an impaired response against HCV antigens while keeping immune competence for other antigens. We hypothesized that expression of HCV proteins in infected dendritic cells (DC) might impair their antigen-presenting function, leading to a defective anti-HCV T-cell immunity. To test this hypothesis, DC from normal donors were transduced with an adenovirus coding for HCV core and E1 proteins and these cells (DC-CE1) were used to stimulate T lymphocytes. DC-CE1 were poor stimulators of allogeneic reactions and of autologous primary and secondary proliferative responses. Autologous T cells stimulated with DC-CE1 exhibited a pattern of incomplete activation characterized by enhanced CD25 expression but reduced interleukin 2 production. The same pattern of incomplete lymphocyte activation was observed in CD4(+) T cells responding to HCV core in patients with chronic HCV infection. However, CD4(+) response to HCV core was normal in patients who cleared HCV after alpha interferon therapy. Moreover, a normal CD4(+) response to tetanus toxoid was found in both chronic HCV carriers and patients who had eliminated the infection. Our results suggest that expression of HCV structural antigens in infected DC disturbs their antigen-presenting function, leading to incomplete activation of anti-HCV-specific T cells and chronicity of infection. However, presentation of unrelated antigens by noninfected DC would allow normal T-cell immunity to other pathogens.
丙型肝炎病毒（HCV）感染患者对HCV抗原的反应受损，而对其他抗原仍保持免疫能力。我们推测，感染的树突状细胞（DC）中HCV蛋白的表达可能会损害其抗原呈递功能，导致抗HCV T细胞免疫缺陷。为了验证这一假设，用编码HCV核心蛋白和E1蛋白的腺病毒转导来自正常供体的DC，并使用这些细胞（DC-CE1）刺激T淋巴细胞。DC-CE1对同种异体反应以及自体初次和二次增殖反应的刺激能力较差。用DC-CE1刺激的自体T细胞表现出不完全激活的模式，其特征是CD25表达增强但白细胞介素2产生减少。在慢性HCV感染患者中，对HCV核心蛋白产生反应的CD4(+) T细胞也观察到相同的不完全淋巴细胞激活模式。然而，在接受α干扰素治疗后清除HCV的患者中，对HCV核心蛋白的CD4(+)反应正常。此外，在慢性HCV携带者和已清除感染的患者中，对破伤风类毒素的CD4(+)反应均正常。我们的结果表明，感染的DC中HCV结构抗原的表达会干扰其抗原呈递功能，导致抗HCV特异性T细胞的不完全激活和感染的慢性化。然而，未感染的DC对无关抗原的呈递将使针对其他病原体的T细胞免疫正常。
