Decreased expression of CD28 coincides with the down-modulation of CD3zeta and augmentation of caspase-3 activity in T cells from hepatocellular carcinoma-bearing patients and hepatitis C virus-infected patients.
OBJECTIVE
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.


CONCLUSIONS
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.
Maki
Akira
A
First Department of Surgery, School of Medicine, Yamanashi University, Yamanashi, Japan. am99d06@stu.yamanashi-med.ac.jp
Matsuda
Masanori
M
Asakawa
Masami
M
Kono
Hiroshi
H
Fujii
Hideki
H
Matsumoto
Yoshiro
Y
D000368:Aged; D018106:CD28 Antigens / Q000096:biosynthesis*; D017252:CD3 Complex / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
D018106:CD28 Antigens; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases