Rapid changes in peripheral lymphocyte concentrations during interferon-free treatment of chronic hepatitis C virus infection.
Rapid changes in peripheral lymphocyte concentrations during interferon-free treatment of chronic hepatitis C virus infection.
复制标题
DOI：
10.1002/hep4.1074
复制
发表时间：
2017-09
影响因子：
5.1
通讯作者：
Kottilil S
中科院分区：
文献类型：
--
作者：
Meissner EG;Kohli A;Higgins J;Lee YJ;Prokunina O;Wu D;Orr C;Masur H;Kottilil S
用直接作用的抗病毒药物治疗慢性丙型肝炎病毒（HCV）感染会导致病毒载量和肝脏炎症标志物（包括血清趋化因子（C-X-C基序）配体10（CXCL 10）浓度）迅速下降，在大多数情况下，随后会出现持续的病毒学应答。外周血细胞组成是否发生显著的平行变化相对未知。我们假设治疗期间外周血的纵向特征将提供对细胞迁移和免疫激活的深入了解，这将对理解HCV治疗前后的宿主免疫力产生影响，并可能与HCV清除有关。我们通过流式细胞术分析了参加两项直接作用抗病毒临床试验的95名受试者的纵向外周先天性和适应性免疫细胞群，并检查了43名患者T淋巴细胞上的趋化因子受体表达。在开始治疗的1 - 2周内，观察到外周分化抗原4阳性（CD 4+）和CD 8 + T淋巴细胞的浓度显著增加，但未观察到单核细胞或自然杀伤细胞。与这些变化相一致的是，具有活化表型（人类白细胞抗原[HLA] DR+和CD 38+）的CD 4+和CD 8 + T淋巴细胞的百分比降低，趋化因子（C-X-C基序）受体3（CXCL 10的趋化因子受体）的T淋巴细胞表面表达增加。结论：在HCV感染的直接作用抗病毒治疗期间，外周细胞群发生快速变化，这可能与由于炎症和趋化因子受体信号传导改变而导致的组织淋巴细胞的肝外排有关，为HCV感染期间宿主免疫和病毒清除之间的关系提供了重要见解。（Hepatology Communications 2017;1：586-594）
Treatment of chronic hepatitis C virus (HCV) infection with direct‐acting antivirals results in a rapid decline in viral load and markers of hepatic inflammation, including serum chemokine (C‐X‐C motif) ligand 10 (CXCL10) concentration, which is followed in most cases by a sustained virologic response. Whether parallel changes of significance occur in the cellular composition of peripheral blood is relatively unknown. We hypothesized that longitudinal characterization of peripheral blood during treatment would provide insight into cellular migration and immune activation, which would have implications for understanding host immunity both before and after HCV treatment and may relate to HCV clearance. We analyzed longitudinal peripheral innate and adaptive immune cell populations by flow cytometry from 95 subjects enrolled in two direct‐acting antiviral clinical trials and examined chemokine receptor expression on T lymphocytes in 43 patients. Within 1‐2 weeks of initiating treatment, significant increases were observed in the concentration of peripheral cluster of differentiation 4–positive (CD4+) and CD8+ T lymphocytes but not monocyte or natural killer cells. In tandem with these changes, the percent of both CD4+ and CD8+ T lymphocytes with an activated phenotype (human leukocyte antigen [HLA] DR+ and CD38+) decreased, and T‐lymphocyte surface expression of chemokine (C‐X‐C motif) receptor 3, the chemokine receptor for CXCL10, increased. Conclusion: Rapid changes in peripheral cellular populations occur during direct‐acting antiviral treatment of HCV infection, which could potentially relate to hepatic efflux of tissue lymphocytes due to altered inflammation and chemokine receptor signaling, providing critical insight into the relationship between host immunity and viral clearance during HCV infection. (Hepatology Communications 2017;1:586–594)
登录
查看更多内容
黑猩猩使用无干扰素抗病毒疗法治愈慢性丙型肝炎后的 T 细胞免疫和丙型肝炎病毒再感染。
影响因子：
13.5
作者：
Callendret, Benoit;Eccleston, Heather B.;Hall, Shelby;Satterfield, William;Capone, Stefania;Folgori, Antonella;Cortese, Riccardo;Nicosia, Alfredo;Walker, Christopher M.
通讯作者：
Walker, Christopher M.
影响因子：
15.9
作者：
Meissner, Eric G.;Wu, David;Kottilil, Shyamasundaran
通讯作者：
Kottilil, Shyamasundaran
影响因子：
25.7
作者：
Midgard, Havard;Bjoro, Benedikte;Dalgard, Olav
通讯作者：
Dalgard, Olav
影响因子：
6.4
作者：
Spaan, Michelle;Claassen, Mark A. A.;Boonstra, Andre
通讯作者：
Boonstra, Andre
影响因子：
11.8
作者：
Kattakuzhy, Sarah;Wilson, Eleanor;Kottilil, Shyamasundaran
通讯作者：
Kottilil, Shyamasundaran