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利巴韦林不会损害 Foxp3(+)CD4(+)CD25(+)调节性 T 细胞的抑制活性。

Ribavirin Does Not Impair the Suppressive Activity of Foxp3(+)CD4(+)CD25(+) Regulatory T Cells.

机构信息

Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea.

出版信息

Immune Netw. 2013 Feb;13(1):25-9. doi: 10.4110/in.2013.13.1.25. Epub 2013 Feb 28.

DOI:10.4110/in.2013.13.1.25
PMID:23559897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3607707/
Abstract

Ribavirin is an antiviral drug used in combination with pegylated interferon-α (IFN-α) for the treatment of hepatitis C virus (HCV) infection. Recently, ribavirin was reported to inhibit the suppressive activity of regulatory T (Treg) cells. In the present study, we re-evaluated the effect of ribavirin on Foxp3(+)CD4(+)CD25(+) Treg cells from normal donors. First, we examined the expression of CTLA-4 and CD39, which are known to play a role in the suppressive function of Treg cells. We found that ribavirin treatment did not modulate the expression of CTLA-4 and CD39 in Treg cells. We also studied the effect of ribavirin on Treg cells in the presence of IFN-α; however, the expression of CTLA-4 and CD39 in Treg cells was not changed by ribavirin in the presence of IFN-α. Next, we directly evaluated the effect of ribavirin on the suppressive activity of Treg cells in the standard Treg suppression assay, by co-culturing CFSE-labeled non-Treg CD4(+) T cells with purified Treg cells. We found that ribavirin did not attenuate the suppressive activity of Treg cells. Taken together, while ribavirin reversed Treg cell-mediated suppression of effector T cells in the previous study, we herein demonstrate that ribavirin does not impair the suppressive activity of Treg cells.

摘要

利巴韦林是一种抗病毒药物,与聚乙二醇干扰素-α(IFN-α)联合用于治疗丙型肝炎病毒(HCV)感染。最近,有报道称利巴韦林能抑制调节性 T(Treg)细胞的抑制活性。在本研究中,我们重新评估了利巴韦林对来自正常供体的 Foxp3(+)CD4(+)CD25(+)Treg 细胞的影响。首先,我们检测了 CTLA-4 和 CD39 的表达,已知它们在 Treg 细胞的抑制功能中发挥作用。我们发现利巴韦林处理不会调节 Treg 细胞中 CTLA-4 和 CD39 的表达。我们还研究了 IFN-α 存在下利巴韦林对 Treg 细胞的影响;然而,在 IFN-α 存在下,利巴韦林并没有改变 Treg 细胞中 CTLA-4 和 CD39 的表达。接下来,我们通过共培养 CFSE 标记的非 Treg CD4(+)T 细胞与纯化的 Treg 细胞,直接评估利巴韦林对 Treg 细胞抑制活性的影响。我们发现利巴韦林并没有减弱 Treg 细胞的抑制活性。综上所述,虽然利巴韦林在前一项研究中逆转了 Treg 细胞对效应 T 细胞的抑制作用,但我们在此证明利巴韦林不会损害 Treg 细胞的抑制活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1898/3607707/4a141f63e92b/in-13-25-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1898/3607707/d5996662ab45/in-13-25-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1898/3607707/4a141f63e92b/in-13-25-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1898/3607707/d5996662ab45/in-13-25-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1898/3607707/4a141f63e92b/in-13-25-g002.jpg

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本文引用的文献

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PLoS One. 2012;7(7):e42094. doi: 10.1371/journal.pone.0042094. Epub 2012 Jul 27.
2
Ribavirin for the treatment of chronic hepatitis C virus infection: a review of the proposed mechanisms of action.利巴韦林治疗慢性丙型肝炎病毒感染:作用机制的研究进展。
Curr Opin Virol. 2011 Dec;1(6):590-8. doi: 10.1016/j.coviro.2011.10.030. Epub 2011 Nov 29.
3
Mechanism of action of ribavirin in a novel hepatitis C virus replication cell system.
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Virus Res. 2011 Apr;157(1):61-70. doi: 10.1016/j.virusres.2011.02.005. Epub 2011 Feb 12.
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Ribavirin potentiates interferon action by augmenting interferon-stimulated gene induction in hepatitis C virus cell culture models.利巴韦林通过增强丙型肝炎病毒细胞培养模型中干扰素刺激基因的诱导作用增强干扰素的作用。
Hepatology. 2011 Jan;53(1):32-41. doi: 10.1002/hep.23985. Epub 2010 Oct 26.
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Ribavirin as an anti-cancer therapy: acute myeloid leukemia and beyond?利巴韦林作为一种抗癌疗法:急性髓细胞白血病及其他?
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