Decreased CD3 zeta molecules of T lymphocytes from patients with hepatocellular carcinoma associated with hepatitis C virus.
Most hepatocellular carcinomas (HCC) occur in chronic liver disease. Under such conditions, an impaired cellular immune response is often observed, but the mechanisms of this deficiency are unclear. The down-modulation of CD3 zeta (a key molecule in signal-transducing factor of T cell receptor) leads to a reduction in the function of T cells. In this study, we demonstrated the decreased expression of CD3 zeta on T cells from hepatitis C virus (HCV) infected hosts and HCC patients and clarified the correlation between the expression of CD3 zeta and tumor progression. Flowcytometrical analysis of CD3 zeta on peripheral T lymphocytes from 12 HCV infected hosts and 36 HCC bearing patients showed a significantly lower CD3 zeta expression than normal controls. Compared with tumor infiltrating T lymphocytes (TIL), intrahepatic T lymphocytes (IHL) and peripheral T lymphocytes (PBL) from 11 HCC bearing patients, the expression of CD3 zeta on TIL was significantly lower than PBL, and the expression level of CD3 zeta on IHL was almost equal to that on TIL. These results suggest that the down-modulation of CD3 zeta of T lymphocytes in HCV infected hosts may be one of the reasons why multicentric occurrence and intrahepatic metastasis occur more frequently in HCC patients than another malignancies.
Maki
Akira
A
First Department of Surgery, Yamanashi Medical Collage, 1110 Shimokatou, Tamaho, 409-3898, Yamanashi, Japan
Matsuda
Masanori
M
Asakawa
Masami
M
Kono
Hiroshi
H
Fujii
Hideki
H
Matsumoto
Yoshiro
Y