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人β-干扰素介导的HTLV-I感染早期阶段的体外抑制

Depression of early phase of HTLV-I infection in vitro mediated by human beta-interferon.

作者信息

D'Onofrio C, Perno C F, Mazzetti P, Graziani G, Calio' R, Bonmassar E

机构信息

Department of Experimental Medicine and Biochemical Sciences, II University of Rome, Italy.

出版信息

Br J Cancer. 1988 May;57(5):481-8. doi: 10.1038/bjc.1988.111.

DOI:10.1038/bjc.1988.111
PMID:2899440
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2246394/
Abstract

Natural human interferon beta (beta-IFN) was tested during the early phase of in vitro infection with HTLV-I virus of human cord blood mononuclear cells (CBL), to evaluate whether its antiviral and immunomodulating effects might prevent spreading of infection in the host. beta-IFN was found to reduce HTLV-I transmission and integration in CBL cultures. Moreover, beta-IFN had no effect in preventing virus transmission and integration in K562 and a very limited effect in HL60 and Molt-4 human tumour lines, suggesting a cell-type specific mode of action. beta-IFN induced a 'priming' response on CBL, since overnight pretreatment of recipient cells or one single treatment at the onset of the coculture were almost equally effective in protecting against HTLV-I infection. During the early days post infection (p.i.), IFN-treated CBL showed a pattern of phenotypic markers that was closer to that of non-infected CBL. In contrast, untreated CBL exposed to HTLV-I showed a percent increase of Tac+, M3+ and Leu 11+ subpopulations. Cell-mediated immune responses of CBL were depressed after coculturing with HTLV-I producer MT-2 cells. beta-IFN was able to boost the cell-mediated cytotoxicity of fresh and infected CBL against both K562 and MT-2 target cells. Leukocyte blastogenesis in mixed lymphocyte/tumour cell cultures, evaluated in terms of 3H-thymidine incorporation during the first week p.i., was also enhanced by IFN when macrophages and lymphocytes were reconstituted at an optimal 1:20 ratio. It is conceivable that this overall enhancement of the immune response induced by beta-IFN could contribute to reduce HTLV-I infection in vitro.

摘要

在人脐带血单核细胞(CBL)受到人类嗜T淋巴细胞病毒I型(HTLV-I)病毒体外感染的早期阶段,对天然人β干扰素(β-IFN)进行了测试,以评估其抗病毒和免疫调节作用是否可能阻止感染在宿主体内传播。发现β-IFN可减少HTLV-I在CBL培养物中的传播和整合。此外,β-IFN在阻止病毒在K562细胞中的传播和整合方面没有作用,在HL60和Molt-4人肿瘤细胞系中的作用非常有限,这表明其作用方式具有细胞类型特异性。β-IFN对CBL诱导了一种“预激发”反应,因为对受体细胞进行过夜预处理或在共培养开始时进行单次处理在预防HTLV-I感染方面几乎同样有效。在感染后的早期,经IFN处理的CBL表现出的表型标志物模式更接近未感染的CBL。相反,暴露于HTLV-I的未处理CBL显示Tac+、M3+和Leu 11+亚群的百分比增加。与HTLV-I产生细胞MT-2细胞共培养后,CBL的细胞介导免疫反应受到抑制。β-IFN能够增强新鲜的和感染的CBL对K562和MT-2靶细胞的细胞介导细胞毒性。当巨噬细胞和淋巴细胞以最佳的1:20比例重建时,在感染后第一周通过3H-胸苷掺入评估的混合淋巴细胞/肿瘤细胞培养物中的白细胞增殖也被IFN增强。可以想象,β-IFN诱导的这种免疫反应的总体增强可能有助于在体外减少HTLV-I感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0761/2246394/f0b7e8232d54/brjcancer00139-0042-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0761/2246394/eb724148a8c2/brjcancer00139-0042-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0761/2246394/f0b7e8232d54/brjcancer00139-0042-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0761/2246394/eb724148a8c2/brjcancer00139-0042-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0761/2246394/f0b7e8232d54/brjcancer00139-0042-b.jpg

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