Cell-mediated immune responses observed after the adoptive transfer of HCV-primed splenocytes in an HCV transgenic mouse model

Abstract

HCV is a positive stranded RNA virus that infects up to 170 million people worldwide. Chronic infection is established in 80% of the cases and may lead to cirrhosis and hepatocellular carcinomas. A major debate regarding chronic HCV pathogenesis is whether liver damage is host or virus mediated. CD4+ and CD8+ immune responses are needed to control infection but these are often inefficient, resulting in chronic infection. The presence of these responses in chronic infection may contribute to liver pathogenesis. To study the relevance of immune-mediated liver damage, we created an immunization regimen which elicited humoral and cellular immune responses in B6C3F1 mice. HCV-primed donor splenocytes were stained with CFSE and transferred to a CE1E2 HCV Tg mouse model. Donor cells were recovered in various organs eight days following the transfer. HCV-primed CD4+ and CD8+ T cells selectively accumulated in the liver of the Tg mice where the CE1E2 transgene is predominantly expressed and caused liver pathology under the form of lymphocyte infiltration. The accumulation of these cells indicates a homing mechanism to this organ and a role in the development of liver pathologies. Further studies are required to unearth the mechanisms behind cellular trafficking and cell-mediated immune damage.