Center for Infectious Disease and Vaccine Research; Graduate School of Biomedical Sciences, Clinical and Population Health Research Program; Department of Medicine
Alanine Transaminase; Antigens, CD; Aspartate Aminotransferases; Drug Therapy, Combination; Flow Cytometry; Hepatitis C; Humans; In Situ Hybridization, Fluorescence; Interferon-alpha; Ribavirin; T-Lymphocytes; *Telomere; Viral Load
Cells | Life Sciences | Medicine and Health Sciences | Therapeutics | Women's Studies
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.
Telomere length, T cells, Cytotoxic T cells, Memory T cells, Interferons, Telomeres, Body mass index, Hepatitis C virus
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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.
DOI of Published Version
PLoS One. 2011;6(8):e20922. Epub 2011 Aug 4. Link to article on publisher's site
O'Bryan, Joel M.; Potts, James A.; Bonkovsky, Herbert L.; Mathew, Anuja; and Rothman, Alan L., "Extended interferon-alpha therapy accelerates telomere length loss in human peripheral blood T lymphocytes" (2011). Women’s Health Research Faculty Publications. 533.