PATHOGENETIC EFFECTOR FUNCTION OF CD4-POSITIVE T-HELPER-1 CELLS IN HEPATITIS-B VIRUS TRANSGENIC MICE

The pathogenetic effector functions of hepatitis B virus (HBV)-specifi c CD4(+), Th1 cells were analyzed in two inbred lineages of HBV transg enic mice, one of which overexpresses the HBV large envelope protein r endering the hepatocytes hypersensitive to the cytopathic effects of I FN-gamma, and another that expresses all of the HBV proteins and repli cates the virus in the liver. Transfer of HBV envelope-specific Th1 ce lls resulted in recognition of viral Ag expressed by hepatic nonparenc hymal cells, cytokine release, and a transient necroinflammatory liver disease in both lineages. The liver disease was very severe in the IF N-gamma-sensitive lineage, and it was less severe in the lineage that replicates the HBV genome; nonetheless, in this lineage the Th1 cytoki nes produced by these cells suppressed viral replication in the liver. These results demonstrate that CD4(+) T cells with a Th1 functional p henotype can perform pathogenetic and antiviral effector functions in vivo. This suggests that CD4(+) T cells can contribute directly to dis ease pathogenesis and inhibit viral replication during HBV infection.