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干扰素诱导静息T细胞的表型变化:Ly-6抗原表达显著增强。

Phenotypic changes induced by interferon in resting T cells: major enhancement of Ly-6 antigen expression.

作者信息

Dumont F J, Palfree R G, Coker L Z

出版信息

J Immunol. 1986 Jul 1;137(1):201-10.

PMID:2423601
Abstract

The murine Ly-6 locus controls multiple cell surface antigenic specificities with distinct cellular and tissue distributions. Although the functions of Ly-6 antigens are unknown, several of these antigens represent interesting markers of T cell differentiation and activation. In this work we used a panel of monoclonal antibodies (MAb) in conjunction with flow cytofluorometry (FCF) analysis to investigate the effect of interferon (IFN) on the surface representation of T cell-associated Ly-6 antigens. It was found that in vitro treatment of purified T cells from both C57Bl/6 (Ly-6.2) and BALB/c (Ly-6.1) mice with 10 to 10(4) U IFN-alpha/beta/ml results in a dose-dependent enhancement of Ly-6 antigen expression. This effect was already detectable after 12 to 18 hr and culminated after 48 hr of incubation. Both frequencies and brightness of Ly-6 bearing cells were increased. The most dramatic shifts were observed for the Ly-6A, D, and E antigens, which were augmented by eightfold to 20-fold upon exposure to 10(4) U IFN alpha/beta/ml. Expression of Ly-6C antigens was enhanced by fourfold to sixfold under the same conditions. Immunochemical analyses and use of metabolic inhibitors additionally demonstrated that such IFN-alpha/beta-induced phenotypic alterations of T cells reflect augmented de novo biosynthesis of Ly-6 molecules. Comparison of purified IFN-alpha and IFN-beta revealed that both are equally active in influencing Ly-6. IFN-gamma also enhanced Ly-6 expression but less efficiently than IFN-alpha/beta. Additional experiments were carried out to determine the selectivity of IFN-alpha/beta action on T cell phenotype. These studies demonstrated that IFN-induced Ly-6 enhancement occurs without emergence of interleukin 2 or transferrin receptors. Expression of H-2 and beta 2m antigens, previously known to be sensitive to IFN, was increased but to a much lesser extent than Ly-6. Most other cell surface antigens examined were minimally affected by IFN-alpha/beta with the exception of Ly-11 and Ly-23. Augmentation of these latter markers was lower than for Ly-6 antigens, however. Therefore the Ly-6 locus appears to be preferentially activated by IFN-alpha/beta in resting T cells. Additional exploration of this phenomenon should provide insight into both the biological significance of Ly-6 antigens and the mechanism(s) by which IFN affect T cell functions.

摘要

小鼠Ly-6基因座控制多种细胞表面抗原特异性,这些特异性具有不同的细胞和组织分布。尽管Ly-6抗原的功能尚不清楚,但其中一些抗原是T细胞分化和激活的有趣标志物。在这项工作中,我们使用一组单克隆抗体(MAb)结合流式细胞荧光术(FCF)分析,来研究干扰素(IFN)对T细胞相关Ly-6抗原表面表达的影响。结果发现,用10至10(4) U IFN-α/β/ml体外处理来自C57Bl/6(Ly-6.2)和BALB/c(Ly-6.1)小鼠的纯化T细胞,会导致Ly-6抗原表达呈剂量依赖性增强。这种效应在孵育12至18小时后即可检测到,并在48小时孵育后达到顶峰。携带Ly-6的细胞频率和亮度均增加。观察到Ly-6A、D和E抗原的变化最为显著,暴露于10(4) U IFNα/β/ml后,它们增加了8倍至20倍。在相同条件下,Ly-6C抗原的表达增强了4倍至6倍。免疫化学分析和代谢抑制剂的使用进一步证明,这种IFN-α/β诱导的T细胞表型改变反映了Ly-6分子从头生物合成的增加。纯化的IFN-α和IFN-β的比较表明,两者在影响Ly-6方面同样有效。IFN-γ也增强了Ly-6的表达,但效率低于IFN-α/β。还进行了其他实验以确定IFN-α/β对T细胞表型作用的选择性。这些研究表明,IFN诱导的Ly-6增强发生时,白细胞介素2或转铁蛋白受体并未出现。先前已知对IFN敏感的H-2和β2m抗原的表达增加,但程度远低于Ly-6。除Ly-11和Ly-23外,所检测的大多数其他细胞表面抗原受IFN-α/β的影响极小。然而,后两者标志物的增强低于Ly-6抗原。因此,Ly-6基因座在静息T细胞中似乎优先被IFN-α/β激活。对这一现象的进一步探索应能深入了解Ly-6抗原的生物学意义以及IFN影响T细胞功能的机制。

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Phenotypic changes induced by interferon in resting T cells: major enhancement of Ly-6 antigen expression.干扰素诱导静息T细胞的表型变化:Ly-6抗原表达显著增强。
J Immunol. 1986 Jul 1;137(1):201-10.
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