Decreased expression of CD28 coincides with the down‐modulation of CD3ζ and augmentation of caspase‐3 activity in T cells from hepatocellular carcinoma‐bearing patients and hepatitis C virus‐infected patients

BACKGROUND AND AIM: Hepatitis C virus (HCV) infection causes chronic inflammation and increases the risk of hepatocellular carcinoma (HCC). This immunosuppressive state may be one reason why HCV-infected patients often have multicentric cancers. Therefore, the purpose of the present study was to assess the cellular immune function in HCC-bearing and HCV-infected patients. METHODS: The expression of cluster of differentiation (CD)3zeta, CD28 and caspase-3 activity of peripheral blood T lymphocytes (PBL) from HCC-bearing patients, HCV-infected patients and normal subjects was measured by flow cytometric methods. Furthermore, intrahepatic T lymphocytes (IHL) and tumor-infiltrating T lymphocytes (TIL) from HCC patients were used. RESULTS: Decreased expressions of CD3zeta, CD28 and the augmentation of caspase-3 activity were recognized in PBL from HCC and HCV patients. These phenomena were more dominant in TIL and IHL than in PBL in HCC patients. Furthermore, the down-modulation of CD3zeta and increased caspase-3 activity occurred in CD28 down-modulated T cells. CONCLUSION: These results demonstrate impairment of the cellular immune system in HCC and HCV patients from the viewpoints of the down-modulation of CD3zeta and CD28 on T cells and T-cell apoptosis. In addition, the results imply that the down-modulation of CD3zeta and T-cell apoptosis take place in activated T cells.