期刊
CELLULAR IMMUNOLOGY
卷 269, 期 2, 页码 104-114出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2011.03.011
关键词
HCV; Viral persistence; PD-1; CD127; PD-L1; z-VAD-fmk; Bim; Cytotoxic T lymphocytes; Chronic hepatitis; Apoptosis
资金
- Fiscam [PI-2007/32, MOV-2007_JI/18]
- Fundacion de Investigacion Medica Mutua Madrilena, Spain [2548/2008]
- Instituto de Salud Carlos III [CA07/00157]
- Asociacion de Hepatologia Translacional Spain [AHT10/01]
PD-1 molecule promotes anergy and IL-7 receptor (CD127) induces an anti-apoptotic effect on T cells. Correlation between PD-1/CD127 phenotype and hepatitis C virus (HCV)-specific CD+ cell reactivity in resolved infection (RI) after treatment and persistent HCV-infection (PI) was analysed. Directly ex vivo, PD-1 and CD127 expression on HCV-specific CD8(+) cells displayed a positive and negative correlation, respectively with viraemia. Proliferation after stimulation on PD-1(-)/CD127(+) cells from RI cases was preserved, while it was impaired on PD-1(+)/CD127(-) cells from PI patients. PD1(+)/CD127(+) population was observed in PI, and these maintained expansion ability but they did not target the virus. Frequency of PI cases with HCV-specific CD8(+) cell proliferation increased after anti-PD-L1 and anti-apoptotic treatment. Bim expression on HCV-specific CD8(+) cells from PI patients was enhanced. In conclusion, during chronic HCV infection non-reactive HCV-specific CD8(+) cells targeting the virus are PD-1(+)/CD127(-)/Bim(+). and, blocking apoptosis and PD-1/PD-L1 pathway on them enhances in vitro reactivity. (C) 2011 Elsevier Inc. All rights reserved.
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