title: Extended interferon-alpha therapy accelerates telomere length loss in human peripheral blood T lymphocytes.
abstract: BACKGROUND
  Type I interferons have pleiotropic effects on host cells, including inhibiting telomerase in lymphocytes and antiviral activity. We tested the hypothesis that long-term interferon treatment would result in significant reduction in average telomere length in peripheral blood T lymphocytes.
  
  
  RESULTS
  Using a flow cytometry-based telomere length assay on peripheral blood mononuclear cell samples from the Hepatitis-C Antiviral Long-term Treatment against Cirrhosis (HALT-C) study, we measured T cell telomere lengths at screening and at months 21 and 45 in 29 Hepatitis-C virus infected subjects. These subjects had failed to achieve a sustained virologic response following 24 weeks of pegylated-interferon-alpha plus ribavirin treatment and were subsequently randomized to either a no additional therapy group or a maintenance dose pegylated-IFNα group for an additional 3.5 years. Significant telomere loss in naïve T cells occurred in the first 21 months in the interferon-alpha group. Telomere losses were similar in both groups during the final two years. Expansion of CD8(+)CD45RA(+)CD57(+) memory T cells and an inverse correlation of alanine aminotransferase levels with naïve CD8(+) T cell telomere loss were observed in the control group but not in the interferon-alpha group. Telomere length at screening inversely correlated with Hepatitis-C viral load and body mass index.
  
  
  CONCLUSIONS
  Sustained interferon-alpha treatment increased telomere loss in naïve T cells, and inhibited the accumulation of T cell memory expansions. The durability of this effect and consequences for immune senescence need to be defined.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Joel M
authors.initials: JM
authors.lastname: O'Bryan
authors.forename: James A
authors.initials: JA
authors.lastname: Potts
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: Anuja
authors.initials: A
authors.lastname: Mathew
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D015703:Antigens, CD / Q000276:immunology; D001219:Aspartate Aminotransferases / Q000097:blood; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology / Q000648:ultrastructure*; D016615:Telomere; D019562:Viral Load
chemical_list: D015703:Antigens, CD; D016898:Interferon-alpha; D012254:Ribavirin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase