Extended interferon-alpha therapy accelerates telomere length loss in human peripheral blood T lymphocytes
UMass Chan Affiliations
Department of MedicineGraduate School of Biomedical Sciences, Clinical and Population Health Research Program
Center for Infectious Disease and Vaccine Research
Document Type
Journal ArticlePublication Date
2011-08-04Keywords
Alanine TransaminaseAntigens, CD
Aspartate Aminotransferases
Drug Therapy, Combination
Flow Cytometry
Hepatitis C
Humans
In Situ Hybridization, Fluorescence
Interferon-alpha
Ribavirin
T-Lymphocytes
*Telomere
Viral Load
Telomere length
T cells
Cytotoxic T cells
Memory T cells
Interferons
Telomeres
Body mass index
Hepatitis C virus
Cells
Life Sciences
Medicine and Health Sciences
Therapeutics
Women's Studies
Metadata
Show full item recordAbstract
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. METHODS/PRINCIPAL FINDINGS: 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-IFNalpha group for an additional 3.5 years. Significant telomere loss in naive 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 naive 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/SIGNIFICANCE: Sustained interferon-alpha treatment increased telomere loss in naive 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.Source
PLoS One. 2011;6(8):e20922. Epub 2011 Aug 4. Link to article on publisher's site
DOI
10.1371/journal.pone.0020922Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50998PubMed ID
21829595Related Resources
Rights
Copyright: © 2011 O'Bryan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0020922