Epitopes described in "Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection."

Article Authors:Kazushi Sugimoto; Fusao Ikeda; Jason Stadanlick; Frederick A Nunes; Harvey J Alter; Kyong-Mi Chang
Article Title:Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection.
Reference Detail
Reference ID:1002213
Abstract:Hepatitis C virus (HCV) has a high propensity for persistence. To better define the immunologic determinants of HCV clearance and persistence, we examined the circulating HCV-specific T-cell frequency, repertoire, and cytokine phenotype ex vivo in 24 HCV seropositive subjects (12 chronic, 12 recovered), using 361 overlapping peptides in 36 antigenic pools that span the entire HCV core, NS3-NS5. Consistent with T-cell-mediated control of HCV, the overall HCV-specific type-1 T-cell response was significantly greater in average frequency (0.24% vs. 0.04% circulating lymphocytes, P =.001) and scope (14/36 vs. 4/36 pools, P =.002) among the recovered than the chronic subjects, and the T-cell response correlated inversely with HCV titer among the chronic subjects (R = -0.51, P =.049). Although highly antigenic regions were identified throughout the HCV genome, there was no apparent difference in the overall HCV-specific T-cell repertoire or type-1/type-2 cytokine profile relative to outcome. Notably, HCV persistence was associated with a reversible CD4-mediated suppression of HCV-specific CD8 T cells and with higher frequency of CD4(+)CD25(+) regulatory T cells (7.3% chronic vs. 2.5% recovered, P =.002) that could directly suppress HCV-specific type-1 CD8 T cells ex vivo. In conclusion, we found that HCV persistence is associated with a global quantitative and functional suppression of HCV-specific T cells but not differential antigenic hierarchy or cytokine phenotype relative to HCV clearance. The high frequency of CD4(+)CD25(+) regulatory T cells and their suppression of HCV-specific CD8 T cells ex vivo suggests a novel role for regulatory T cells in HCV persistence.
Affiliations:Department of Medicine, University of Pennsylvania & Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104, USA.
Reference Type:Literature
PubMed ID:14647055
Journal Volume:38
Article Pages:1437-48
Journal ISSN:1527-3350
Article Chemical List:RNA, Viral;Receptors, Interleukin-2
Article MeSH List:Adult; Aged; Amino Acid Sequence; CD4-Positive T-Lymphocytes(immunology); CD8-Positive T-Lymphocytes(immunology); Female; Hepacivirus(immunology); Hepatitis C, Chronic(immunology; virology); Humans; Immune Tolerance; Male; Middle Aged; Molecular Sequence Data; RNA, Viral(blood); Receptors, Interleukin-2(analysis); T-Lymphocytes(immunology); Th1 Cells(immunology)
Curation Last Updated:2015-07-24 20:06:25