Abstract
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 CD8(+) 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.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adult
-
Amino Acid Chloromethyl Ketones / pharmacology
-
Antibodies, Monoclonal / immunology
-
Antibodies, Monoclonal / pharmacology
-
Antigens, CD / immunology
-
Antigens, CD / metabolism*
-
Apoptosis / drug effects
-
Apoptosis / immunology*
-
Apoptosis Regulatory Proteins / metabolism*
-
B7-H1 Antigen
-
Bcl-2-Like Protein 11
-
Cell Count
-
Cell Proliferation / drug effects
-
Female
-
Hepatitis C, Chronic / immunology*
-
Humans
-
Immunophenotyping
-
Interleukin-7 Receptor alpha Subunit / metabolism*
-
Liver / immunology
-
Liver / pathology
-
Lymphocyte Activation / drug effects
-
Lymphocyte Activation / immunology
-
Lymphocyte Count
-
Male
-
Membrane Proteins / metabolism*
-
Middle Aged
-
Programmed Cell Death 1 Receptor
-
Proto-Oncogene Proteins / metabolism*
-
Signal Transduction / drug effects
-
Signal Transduction / immunology
-
T-Lymphocyte Subsets / immunology
-
T-Lymphocyte Subsets / metabolism
-
T-Lymphocyte Subsets / physiology
-
T-Lymphocytes, Cytotoxic / immunology*
-
T-Lymphocytes, Cytotoxic / metabolism
-
T-Lymphocytes, Cytotoxic / pathology
-
Viral Load / immunology
-
Viral Nonstructural Proteins / immunology
Substances
-
Amino Acid Chloromethyl Ketones
-
Antibodies, Monoclonal
-
Antigens, CD
-
Apoptosis Regulatory Proteins
-
B7-H1 Antigen
-
BCL2L11 protein, human
-
Bcl-2-Like Protein 11
-
CD274 protein, human
-
Interleukin-7 Receptor alpha Subunit
-
Membrane Proteins
-
NS3 protein, hepatitis C virus
-
PDCD1 protein, human
-
Programmed Cell Death 1 Receptor
-
Proto-Oncogene Proteins
-
Viral Nonstructural Proteins
-
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone