Adoptive transfer of splenocytes to study cell-mediated immune responses in hepatitis C infection using HCV transgenic mice

In comparison to non-transgenic mice, there was a significant decrease in the percentage of CFSE-labeled CD4+ and CD8+ T cells in transgenic mouse peripheral blood receiving adoptive transfers from immunized donors. Moreover, the percentage of CFSE-labeled CD4+ and CD8+ T cells were significantly higher in the spleen of transgenic and non-transgenic mice when they received splenocytes from non-immunized than from immunized mice. On the other hand, the percentages of CD4+ and CD8+ T cells in the non-transgenic recipient mouse lymph nodes were significantly higher than the transgenic mice when they received the adoptive transfer from immunized donors. Interestingly, livers of transgenic mice that received transfers from immunized mice had a significantly higher percentage of CFSE labeled T cells than livers of non-transgenic mice receiving non-immunized transfers.These results suggest that the T cells from HCV immunized mice recognize the HCV proteins in the liver of the transgenic mouse model and homed to the HCV antigen expression sites. We propose using this model system to study active T cell responses in HCV infection.Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide. The virus causes chronic infection in 80% of acutely HCV-infected patients; a subset of these individuals develop progressive liver injury leading to liver cirrhosis and/or hepatocellular carcinoma [1,2]. Immune responses to HCV play important roles at various stages of the infection. There is emerging evidence that the ability of acutely HCV-infected patients to control the primary HCV infection depends on the vigorous cellular immune reaction to the virus [3]. In the chronic phase of infection, immune responses determine the rate of progression of disease, both by limiting viral replication and by contributing to immunopathology. Livers from chronically HCV-infected individuals show T cell infiltration; however, these cells are not HCV specific and are unable to eradicate