Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
PLoS One. 2011;6(8):e20922. doi: 10.1371/journal.pone.0020922. Epub 2011 Aug 4.
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-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/SIGNIFICANCE: 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.
I 型干扰素对宿主细胞具有多种效应，包括抑制淋巴细胞端粒酶和抗病毒活性。我们检验了这样一个假设，即长期的干扰素治疗会导致外周血 T 淋巴细胞平均端粒长度显著缩短。
方法/主要发现：我们使用基于流式细胞术的外周血单个核细胞样品端粒长度测定法，在慢性丙型肝炎抗病毒长期治疗（HALT-C）研究中，对 29 例丙型肝炎病毒感染患者的筛选、21 个月和 45 个月时的 T 细胞端粒长度进行了测量。这些患者在接受 24 周聚乙二醇干扰素-α联合利巴韦林治疗后未能实现持续病毒学应答，随后被随机分为无额外治疗组或维持剂量聚乙二醇 IFNα 组，再进行 3.5 年的治疗。在干扰素-α组中，在最初的 21 个月内，幼稚 T 细胞的端粒明显丢失。在最后两年中，两组的端粒丢失相似。在对照组中观察到 CD8+CD45RA+CD57+记忆 T 细胞的扩增和丙氨酸氨基转移酶水平与幼稚 CD8+T 细胞端粒丢失呈负相关，但在干扰素-α组中未观察到这种现象。筛选时的端粒长度与丙型肝炎病毒载量和体重指数呈负相关。
结论/意义：持续的干扰素-α治疗增加了幼稚 T 细胞的端粒丢失，并抑制了 T 细胞记忆扩增的积累。这种效应的持久性及其对免疫衰老的影响需要进一步确定。
