Expression of Fas/FasL in CD8+ T and CD3+ Foxp3+ Treg cells--relationship with apoptosis of circulating CD8+ T cells in hepatocellular carcinoma patients.
OBJECTIVE
Dysfunction of the host immune system in cancer patients can be due to a number of factors, including lymphocyte apoptosis. Several studies showed that Foxp3+T cells take part in inducing this process by expressing FasL in tumor patients. However, the relationship between apoptosis, CD8+T cells and Foxp3+T cells in HCC patients is still unclear. The present study was designed to investigate the correlation between apoptosis levels and Fas/FasL expression in CD8+T lymphocytes and Foxp3+T cells in patients with HCC.


METHODS
CD8+T cells and CD3+Foxp3+T cells were tested from peripheral blood of HCC patients and normal controls and subjected to multicolor flow cytometry. The expression of an apoptosis marker (annexin V) and the death receptor Fas in CD8+T cells and FasL in CD3+Foxp3+T cells were evaluated. Serum TGF-β1 levels in patients with HCC were measured by enzyme-linked immunosorbent assay. The relationship between apoptosis and Fas expression, as well as FasL expression in CD3+Foxp3+T cells was then evaluated.


RESULTS
The frequency of CD8+T cells binding annexin V and Fas expression in CD8+T cells, were all higher in HCC patients than normal controls and the proportion of apoptotic CD8+T cells correlated with their Fas expression. Serum TGF-β1 levels correlated inversely with CD3+Foxp3+T cells.


CONCLUSIONS
Fas/FasL interactions might lead to excessive turnover of CD8+T cells and reduce anti-tumor immune responses in patients with HCC. Further investigations of apoptosis induction in Fas+CD8+T cells in vitro are required.
The Third Affiliated Hospital, Harbin Medical University, Harbin, China E-mail : docguocunli@163.com.
Cun-Li
CL
Guo
Xiu-Hua
XH
Yang
Wen
W
Cheng
Yi
Y
Xu
Jie-Bing
JB
Li
Yi-Xin
YX
Sun
Yu-Mei
YM
Bi
Lei
L
Zhang
Qiu-Cheng
QC
Wang
D017209:Apoptosis; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D053222:Fas Ligand Protein / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism*
D017252:CD3 Complex; C491901:FAS protein, human; C505661:FASLG protein, human; C418974:FOXP3 protein, human; D053222:Fas Ligand Protein; D051858:Forkhead Transcription Factors; D019014:fas Receptor