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

Turaya Naas,Nicole Scherling,Rudy Muller,Masoud Ghorbani,Francisco Diaz-Mitoma,Peyman Ghorbani,Catalina Soare

doi:10.1186/1476-5926-9-7

Abstract

BackgroundHepatitis C virus (HCV) is a major cause of chronic hepatitis and a health problem affecting over 170 million people around the world. We previously studied transgenic mice that express HCV Core, Envelope 1 and Envelope 2 proteins predominantly in the liver, resulting in steatosis, liver and lymphoid tumors, and hepatocellular carcinoma. Herein, the immune-mediated cell response to hepatitis C antigens was evaluated by adoptive transfers of carboxyfluorescein succinimidyl ester (CFSE) labelled splenocytes from HCV immunized mice into HCV transgenic mice.ResultsIn 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.ConclusionsThese 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.

Highlights

Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide
Immune response in HCV-immunized donor mice We developed a hepatitis C transgenic mouse model in which the HCV structural proteins are predominantly expressed in the liver [17]
There was a marked increase in the proliferation response of the immunized mouse splenocytes when they were stimulated with HCV Core/E1/E2 or core peptides, as indicated by the decrease in the carboxyfluorescein succinimidyl ester (CFSE) stain intensity

Summary

Introduction

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]. The immunological basis for the inefficiency of the cellular immune response in chronically infected persons is not well understood. The immune-mediated cell response to hepatitis C antigens was evaluated by adoptive transfers of carboxyfluorescein succinimidyl ester (CFSE) labelled splenocytes from HCV immunized mice into HCV transgenic mice

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Results

Discussion

Conclusion