Cutting edge: programmed death-1 expression is increased on immunocytes in chronic hepatitis C virus and predicts failure of response to antiviral therapy: race-dependent differences.
Up-regulation of programmed death-1 (PD-1) identifies exhausted T cells in various mouse and human viral models including chronic hepatitis C virus (HCV) infection, which is characterized by impaired CTL function. A large proportion of patients fail to eradicate HCV with current IFN-based antiviral therapy; in particular, African Americans are less likely to respond, but the mechanisms for these differences are not fully elucidated. In this study, in 72 treatment-naive patients with persistent HCV we found that PD-1 was significantly up-regulated on CD4(+) and CD8(+) T cells, HCV-specific CTLs, and NK cells. Increased PD-1 on HCV-specific CTLs was significantly associated with failed early and sustained virologic response to therapy in African American but not Caucasian American patients. Patients with sustained virologic response showed decreases in PD-1 on total CD4(+) T cells, HCV-specific CTLs, and the CD56(bright) NK subset after therapy completion. Collectively, these data indicate that PD-1 is critical in persistent HCV and successful therapy results in global down-regulation of its expression.
Golden-Mason
Lucy
L
Division of Gastroenterology and Hepatology, Hepatitis C Center, University of Colorado Health Sciences Center and National Jewish Hospital, Aurora, Co 80045, USA.
Klarquist
Jared
J
Wahed
Abdus S
AS
Rosen
Hugo R
HR
D001741:Black or African American / Q000235:genetics; D000483:Alleles; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics*; D000998:Antiviral Agents / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000208:ethnology / Q000276:immunology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D061026:Programmed Cell Death 1 Receptor; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*; D044465:White People / Q000235:genetics
D015703:Antigens, CD; D000998:Antiviral Agents; D051017:Apoptosis Regulatory Proteins; D006680:HLA Antigens; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor