Franco A, Guidotti L G, Hobbs M V, Pasquetto V, Chisari F V
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Immunol. 1997 Aug 15;159(4):2001-8.
The pathogenetic effector functions of hepatitis B virus (HBV)-specific CD4+, Th1 cells were analyzed in two inbred lineages of HBV transgenic mice, one of which overexpresses the HBV large envelope protein rendering the hepatocytes hypersensitive to the cytopathic effects of IFN-gamma, and another that expresses all of the HBV proteins and replicates the virus in the liver. Transfer of HBV envelope-specific Th1 cells resulted in recognition of viral Ag expressed by hepatic nonparenchymal cells, cytokine release, and a transient necroinflammatory liver disease in both lineages. The liver disease was very severe in the IFN-gamma-sensitive lineage, and it was less severe in the lineage that replicates the HBV genome; nonetheless, in this lineage the Th1 cytokines produced by these cells suppressed viral replication in the liver. These results demonstrate that CD4+ T cells with a Th1 functional phenotype can perform pathogenetic and antiviral effector functions in vivo. This suggests that CD4+ T cells can contribute directly to disease pathogenesis and inhibit viral replication during HBV infection.
在两个乙肝病毒（HBV）转基因小鼠近交系中分析了HBV特异性CD4⁺ Th1细胞的致病效应功能，其中一个近交系过表达HBV大包膜蛋白，使肝细胞对IFN-γ的细胞病变效应高度敏感，另一个近交系表达所有HBV蛋白并在肝脏中复制病毒。转移HBV包膜特异性Th1细胞导致两个近交系中肝非实质细胞表达的病毒抗原被识别、细胞因子释放以及短暂的坏死性炎症性肝病。在IFN-γ敏感的近交系中，肝病非常严重，而在复制HBV基因组的近交系中则较轻；尽管如此，在这个近交系中，这些细胞产生的Th1细胞因子抑制了肝脏中的病毒复制。这些结果表明，具有Th1功能表型的CD4⁺ T细胞可在体内发挥致病和抗病毒效应功能。这表明CD4⁺ T细胞可直接促进疾病发病机制，并在HBV感染期间抑制病毒复制。
