The proapoptotic protein Bim is not differentially regulated in CD8+ T cells from resolved or chronic HCV infection

Background: CD8 T cells play an important role in the antiviral immune response against HCV. Nevertheless, these cells fail to control the viral replication in patients with chronic infection either due to mutational escape of the virus in targeted epitopes or a dysfunctional phenotype of virus-specific CD8 T cells. Moreover, deletion of virus-specific CD8 T cells due to premature apoptosis upon their activation in the liver has been suggested. The pro-apoptotic BH3-only protein Bim has been found to be upregulated in CD8+ T cells activated by hepatocytes in mouse models as well as in patients chronically infected with HBV. Here, we addressed whether this molecule also plays a role in in HCV infection. Methods: PBMC were collected from anti-HCV positive injection drug users with chronic or spontaneously resolved HCV infection. From this cohort 13 “resolvers” and 13 “chronics” with detectable CD8 T cells by staining with HLA/peptide-multimers ex vivo were used for this study. The expression of Bim and the activation marker CD38 was analysed on HCV-, CMV- and Flu-specific CD8 T cells ex vivo and after 7 days of antigen-specific expansion via flow cytometry. Results: No significant difference in the expression level of Bim or CD38 could be observed in HCV-specific CD8+ T cells from patients with resolved infection compared to those with chronic infection ex vivo. After 7 days of antigen-specific expansion, both Bim and CD38 were upregulated on antigen-specific CD8 T cells, irrespective of the disease status. Both molecules were also upregulated in bulk CD8 T cells after unspecific activation with anti-CD3. There was also no difference between the Bim expression in HCV-specific CD8 T cells and Flu- or CMV-specific CD8 T cells. Conclusions: The pro-apoptotic molecule Bim is upregulated in CD8 T cells upon their activation, however, we find no evidence for differential regulation in HCV-specific cells from patients with chronic or spontaneously resolved HCV-infection.