Lymphokine and nonlymphokine mRNA levels in stimulated human T cells. Kinetics, mitogen requirements, and effects of cyclosporin A

Lymphokine and nonlymphokine mRNA levels in stimulated human T cells. Kinetics, mitogen requirements, and effects of cyclosporin A
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受刺激的人 T 细胞中淋巴因子和非淋巴因子 mRNA 水平。

DOI:
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发表时间:
1986
影响因子:
15.3
通讯作者:
R. Steinman
R. Steinman
中科院分区:
医学1区
文献类型:
--
作者:
A. Granelli‐Piperno;L. Andrus;R. Steinman

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使用一组DNA探针的北方印迹和斑点印迹来监测有丝分裂原刺激的人T细胞中特异性mRNA的水平。IL-2和IFN mRNA的诱导需要PMA和PHA或OKT 3 mAb的协同作用。与此相反,几个非淋巴因子基因,原癌基因c-fos和c-myc,和IL-2-R基因,无论是PHA或PMA单独诱导。PHA使70 kD热休克蛋白mRNA的本底水平升高,但不影响c-myb mRNA的本底水平。对于诱导的所有mRNA,分离的CD 4和CD 8 T细胞亚群表现相似。外源性IL-2对淋巴因子mRNA影响不大或无影响,但显著增加c-myc、IL-2-R和热休克蛋白mRNA。因此,淋巴因子mRNA的刺激不同于几种诱导型非淋巴因子基因所需的刺激。然而,IL-2和IFN mRNA与c-myc表现出一些重要的相似性。IL-2,IFN,和c-myc mRNA的水平遵循类似的动力学,峰值在3小时,在再刺激的原始细胞和未刺激的T细胞在12小时。随后的下调淋巴因子和c-myc基因被延迟放线菌酮。IL-2,IFN和c-myc mRNA的诱导被免疫抑制药物CsA阻断,但不被非活性类似物CsH阻断,并且这种阻断发生在核转录水平。由于淋巴因子和c-myc基因表达的外源性刺激不同,我们建议,细胞内控制必须共享,以解释其表达动力学和CsA敏感性的相似性。
Northern and dot blotting with a panel of DNA probes were used to monitor the levels of specific mRNAs in mitogen-stimulated human T cells. The induction of IL-2 and IFN mRNAs required the synergistic action of PMA and either PHA or OKT3 mAb. In contrast, several nonlymphokine genes, the protooncogenes c-fos and c-myc, and the IL-2-R gene, were induced by either PHA or PMA alone. PHA increased the background levels of a 70 kD heat shock protein mRNA, but did not affect the observed background of c-myb mRNA. For all mRNAs that were induced, isolated CD4 and CD8 T cell subsets behaved similarly. Exogenous IL-2 had little (IFN) or no (IL-2) effect on lymphokine mRNAs, but significantly increased c-myc, IL-2-R and heat shock protein mRNAs. Therefore, the stimuli for lymphokine mRNAs differed from those required for several inducible nonlymphokine genes. IL-2 and IFN mRNAs exhibited some important similarities with c-myc, however. The levels of IL-2, IFN, and c-myc mRNA followed similar kinetics, peaking at 3 h in restimulated blasts and at 12 h in unstimulated T cells. The subsequent downregulation of lymphokine and c-myc mRNAs was retarded by cycloheximide. The induction of IL-2, IFN, and c-myc mRNAs was blocked by the immunosuppressive drug CsA, but not by the inactive analog CsH, and this block occurred at the level of nuclear transcription. Since the exogenous stimuli for lymphokine and c-myc gene expression differ, we suggest that intracellular controls must be shared to account for the similarities in their kinetics of expression and CsA sensitivity.
通过细胞增殖调节剂调节正常人淋巴细胞中的 c-myc mRNA 水平。
DOI: 10.1073/pnas.82.12.4221
发表时间: 1985
影响因子: 11.1
作者:
Reed,JC;Nowell,PC;Hoover,RG
通讯作者: Hoover,RG
T3 表面分子在人类 T 细胞激活中的作用:T3 依赖性激活导致细胞质游离钙增加。
DOI: 10.1073/pnas.81.13.4169
发表时间: 1984
影响因子: 11.1
作者:
Weiss,A;Imboden,J;Shoback,D;Stobo,J
通讯作者: Stobo,J
DOI: 10.1073/pnas.81.24.7742
发表时间: 1984-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
RAMSAY, G;EVAN, GI;BISHOP, JM
通讯作者: BISHOP, JM