Smyk-Pearson Susan, Tester Ian A, Klarquist Jared, Palmer Brent E, Pawlotsky Jean-Michel, Golden-Mason Lucy, Rosen Hugo R
GI and Hepatology Division, B-158, Academic Office Building 1, 12631 East 17th Ave., Room 7614, P.O. Box 6511, Aurora, CO 80045, USA.
J Virol. 2008 Feb;82(4):1827-37. doi: 10.1128/JVI.01581-07. Epub 2007 Nov 28.
The mechanisms mediating protective immunity to hepatitis C virus (HCV) infection are incompletely understood because early infection in humans is rarely identified, particularly in those individuals who subsequently demonstrate spontaneous virus eradication. We have established a large national network of patients with acute HCV infection. Here, we comprehensively examined total HCV-specific CD4(+) and CD8(+) T-cell responses and identified functional T-cell thresholds that predict recovery. Interestingly, we found that the presence of HCV-specific cytotoxic T lymphocytes (CTLs) that can proliferate, exhibit cytotoxicity, and produce gamma interferon does not ensure recovery, but whether these CTLs were primed in the presence or absence of CD4(+) T-cell help (HCV-specific interleukin-2 production) is a critical determinant. These results have important implications for early prediction of the virologic outcome following acute HCV and for the development of novel immunotherapeutic approaches.
介导对丙型肝炎病毒（HCV）感染保护性免疫的机制尚未完全明确，因为人类早期感染很少被识别，尤其是那些随后能自发清除病毒的个体。我们建立了一个大型的全国急性HCV感染患者网络。在此，我们全面检测了HCV特异性CD4(+)和CD8(+) T细胞反应，并确定了预测康复的功能性T细胞阈值。有趣的是，我们发现能够增殖、表现出细胞毒性并产生γ干扰素的HCV特异性细胞毒性T淋巴细胞（CTL）的存在并不能确保康复，而这些CTL是否在有或无CD4(+) T细胞辅助（HCV特异性白细胞介素-2产生）的情况下启动是一个关键决定因素。这些结果对急性HCV感染后病毒学结果的早期预测以及新型免疫治疗方法的开发具有重要意义。
