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环孢素A对干扰素和丝裂原诱导的Ly-6A抗原具有不同影响,提示活化T细胞中Ly-6A表达的自分泌调节。

Divergent effects of cyclosporine A on interferon- and mitogen-induced Ly-6A antigen suggest autocrine regulation of Ly-6A expression in activated T cells.

作者信息

Dumont F J

出版信息

Cell Immunol. 1987 Apr 1;105(2):355-65. doi: 10.1016/0008-8749(87)90083-9.

DOI:10.1016/0008-8749(87)90083-9
PMID:2436810
Abstract

The murine Ly-6A cell surface antigen is normally present on a minor subset of mature T cells. This marker has been shown to become highly expressed on mitogen-activated T cells. We found that expression of Ly-6A is also markedly increased in resting T cells by incubation with IFN-alpha/beta or IFN-gamma. Here, we compared the effect of the immunosuppressant cyclosporine A (CsA) on Ly-6A induction by IFN and concanavalin A (Con A). The augmentation of Ly-6A expression produced by treatment of T cells with IFN-alpha/beta or IFN-gamma was found not to be affected by CsA concentrations up to 2 micrograms/ml. In contrast, at doses as low as 50 ng/ml, CsA prevented the enhancement of Ly-6A expression in Con A-treated T-cell cultures. Culture supernatant transfer experiments were performed to further explore this effect of CsA. It was found that supernatants from Con A-activated T cells enhanced Ly-6A expression in resting T cells. This activity could be neutralized with an anti-IFN-gamma monoclonal antibody. Supernatants from T cells treated with Con A in presence of CsA lacked Ly-6A-enhancing activity. Taken together, these data suggest that the inhibition by CsA of Ly-6A induction in Con A-treated T cells reflects the known inhibitory effects of the drug on IFN-gamma secretion. This may imply the existence in T cells of an autocrine circuit involving IFN-gamma and regulating Ly-6A expression.

摘要

小鼠Ly-6A细胞表面抗原通常存在于一小部分成熟T细胞上。已证明该标志物在有丝分裂原激活的T细胞上高度表达。我们发现,通过与IFN-α/β或IFN-γ孵育,静止T细胞中Ly-6A的表达也会显著增加。在此,我们比较了免疫抑制剂环孢素A(CsA)对IFN和伴刀豆球蛋白A(Con A)诱导Ly-6A的影响。发现用IFN-α/β或IFN-γ处理T细胞所产生的Ly-6A表达增强不受高达2微克/毫升的CsA浓度影响。相反,低至50纳克/毫升的剂量时,CsA可阻止Con A处理的T细胞培养物中Ly-6A表达的增强。进行了培养上清液转移实验以进一步探究CsA的这种作用。发现Con A激活的T细胞的上清液可增强静止T细胞中Ly-6A的表达。这种活性可用抗IFN-γ单克隆抗体中和。在CsA存在下用Con A处理的T细胞的上清液缺乏Ly-6A增强活性。综上所述,这些数据表明CsA对Con A处理的T细胞中Ly-6A诱导的抑制反映了该药物对IFN-γ分泌的已知抑制作用。这可能意味着T细胞中存在一个涉及IFN-γ并调节Ly-6A表达的自分泌回路。

相似文献

1
Divergent effects of cyclosporine A on interferon- and mitogen-induced Ly-6A antigen suggest autocrine regulation of Ly-6A expression in activated T cells.环孢素A对干扰素和丝裂原诱导的Ly-6A抗原具有不同影响,提示活化T细胞中Ly-6A表达的自分泌调节。
Cell Immunol. 1987 Apr 1;105(2):355-65. doi: 10.1016/0008-8749(87)90083-9.
2
The augmentation of surface Ly-6A/E molecules in activated T cells is mediated by endogenous interferon-gamma.活化T细胞表面Ly-6A/E分子的增加是由内源性干扰素-γ介导的。
J Immunol. 1987 Dec 15;139(12):4088-95.
3
Selective up-regulation by interferon-gamma of surface molecules of the Ly-6 complex in resting T cells: the Ly-6A/E and TAP antigens are preferentially enhanced.γ干扰素对静息T细胞中Ly-6复合体表面分子的选择性上调:Ly-6A/E和TAP抗原优先增强。
Eur J Immunol. 1987 Aug;17(8):1183-91. doi: 10.1002/eji.1830170816.
4
Induction of Ly-6A/E expression by murine lymphocytes after in vivo immunization is strictly dependent upon the action of IFN-alpha/beta and/or IFN-gamma.体内免疫后小鼠淋巴细胞诱导Ly-6A/E表达严格依赖于IFN-α/β和/或IFN-γ的作用。
Int Immunol. 1991 Sep;3(9):845-52. doi: 10.1093/intimm/3.9.845.
5
Tumor necrosis factor synergistically acts with IFN-gamma to regulate Ly-6A/E expression in T lymphocytes, thymocytes and bone marrow cells.肿瘤坏死因子与γ干扰素协同作用,调节T淋巴细胞、胸腺细胞和骨髓细胞中Ly-6A/E的表达。
J Immunol. 1989 Mar 15;142(6):1929-36.
6
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.
7
Ly-6 A/E antigen of murine T cells is associated with a distinct pathway of activation. Requirements for interferon and exogenous interleukin 2.小鼠T细胞的Ly-6 A/E抗原与一条独特的激活途径相关。对干扰素和外源性白细胞介素2的需求。
Eur J Immunol. 1988 Jun;18(6):937-42. doi: 10.1002/eji.1830180616.
8
Subsets of activated CD4 T lymphocytes refractory for secretion of IL-2 are distinguished by expression of Ly-6A/E in BALB/c mice.在BALB/c小鼠中,对白细胞介素-2分泌具有抗性的活化CD4 T淋巴细胞亚群可通过Ly-6A/E的表达来区分。
J Immunol. 1993 Dec 1;151(11):5918-29.
9
Unexpected up-regulation of gene expression by cyclosporin A and FK-506 in a T-cell lymphoma: both immunosuppressants augment Ly-6E antigen induction by interferon-gamma in the presence of ionomycin.环孢素A和他克莫司(FK-506)在T细胞淋巴瘤中意外上调基因表达:在离子霉素存在的情况下,这两种免疫抑制剂均增强γ干扰素诱导的Ly-6E抗原表达。
Int J Immunopharmacol. 1991;13(8):1187-99. doi: 10.1016/0192-0561(91)90170-c.
10
Interferon-alpha/beta enhances the expression of Ly-6 antigens on T cells in vivo and in vitro.α/β干扰素在体内和体外均可增强T细胞上Ly-6抗原的表达。
Eur J Immunol. 1986 Jul;16(7):735-40. doi: 10.1002/eji.1830160704.

引用本文的文献

1
The T-cell activating protein (TAP) is up-regulated by endogenous IFN-gamma in activated T cells.T细胞激活蛋白(TAP)在活化的T细胞中被内源性γ干扰素上调。
Immunology. 1988 Jun;64(2):267-71.