Vertuani Simona, Bazzaro Martina, Gualandi Guido, Micheletti Fabiola, Marastoni Mauro, Fortini Cinzia, Canella Alessandro, Marino Michele, Tomatis Roberto, Traniello Serena, Gavioli Riccardo
Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Ferrara, Italy.
Eur J Immunol. 2002 Jan;32(1):144-54. doi: 10.1002/1521-4141(200201)32:1<144::AID-IMMU144>3.0.CO;2-X.
The majority of hepatitis C virus (HCV)-infected individuals fail to resolve the infection and become chronically infected despite the presence of HCV-specific CTL responses directed to different HCV-derived peptide antigens. Only a minority of individuals is able to clear the virus by mounting efficient CTL responses early after acute infection, but at present it is not clear whether viral clearance is associated with CTL responses of defined specificity. To elucidate those responses associated with improvement of the disease, we analyzed CTL responses to 16 different HLA-A2-presented, HCV-derived epitopes in 12 chronically infected patients, 14 chronically infected patients treated with interferon-alpha, and in one patient with acute symptomatic disease. We show here that the majority of chronically infected individuals present CTL responses directed to an NS4-derived peptide antigen (amino acids 1789-1797). Treated patients presented stronger HCV-specific CTL responses and therapy-induced changes in CTL target choice. In particular, 13 out of 14 individuals responded to an NS3-derived epitope (amino acids 1073-1081). By longitudinal analysis we show that five individuals responding to IFN-alpha therapy with decreases in alanine aminotransferase levels presented a strong CTL activity directed to the NS3-derived epitope. One patient that spontaneously resolved the infection presented a generally strong CTL activity specific for HCV-derived epitopes with a dominant response to the NS3-derived peptide antigen. This suggests that CTL responses directed to this NS3-derived antigen may be beneficial for the control of HCV infection. Improvement of these responses may represent a therapeutic intervention in chronic HCV infection.
尽管存在针对不同丙型肝炎病毒（HCV）衍生肽抗原的HCV特异性CTL反应，但大多数HCV感染个体仍无法清除感染并转为慢性感染。只有少数个体能够在急性感染后早期通过产生有效的CTL反应清除病毒，但目前尚不清楚病毒清除是否与特定特异性的CTL反应相关。为了阐明与疾病改善相关的那些反应，我们分析了12例慢性感染患者、14例接受α干扰素治疗的慢性感染患者以及1例急性症状性疾病患者对16种不同的由HLA - A2呈递的HCV衍生表位的CTL反应。我们在此表明，大多数慢性感染个体呈现针对NS4衍生肽抗原（氨基酸1789 - 1797）的CTL反应。接受治疗的患者呈现出更强的HCV特异性CTL反应以及治疗诱导的CTL靶标选择变化。特别是，14例个体中有13例对NS3衍生表位（氨基酸1073 - 1081）有反应。通过纵向分析我们表明，5例对α干扰素治疗有反应且丙氨酸转氨酶水平降低的个体呈现出针对NS3衍生表位的强烈CTL活性。1例自发清除感染的患者呈现出对HCV衍生表位普遍强烈的CTL活性，对NS3衍生肽抗原的反应占主导。这表明针对这种NS3衍生抗原的CTL反应可能有利于控制HCV感染。改善这些反应可能代表对慢性HCV感染的一种治疗干预。
