Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones.
Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones.
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DOI：
10.1084/jem.170.6.2081
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发表时间：
1989-12-01
期刊：
影响因子：
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通讯作者：
Mosmann TR
中科院分区：
文献类型：
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作者：
Fiorentino DF;Bond MW;Mosmann TR
细胞因子合成抑制因子（CSIF）由Th 2克隆响应于Con A或抗原刺激而分泌，但在Con A诱导的Th 1克隆的上清液中不存在。CSIF可抑制Th 1细胞对抗原和APC的反应产生IL-2、IL-3、LPS/TNF、IFN-γ和粒细胞-巨噬细胞CSF（GM-CSF），但对Th 2细胞因子的合成无明显影响。转化生长因子β（TGF-β）也抑制IFN-γ的产生，尽管不如CSIF有效，而IL-2和IL-4部分拮抗CSIF的活性。CSIF对细胞因子合成的抑制是不完全的，因为早期细胞因子合成（8小时前）没有受到显著影响，而后期合成受到强烈抑制。在CSIF的存在下，IFN-γ mRNA水平在刺激后8小时轻微降低，并且在刺激后12小时强烈降低。CSIF对细胞因子表达的抑制不是由于Th 1细胞活力的普遍降低，因为肌动蛋白mRNA水平没有降低，并且抗原刺激的细胞响应于IL-2的增殖不受影响。生物化学表征、mAb和重组或纯化的细胞因子显示CSIF不同于IL-1、IL-2、IL-3、IL-4、IL-5、IL-6、IL-7、IFN-γ、GM-CSF、TGF-β、TNF、LT和P40。CSIF在Th 1和Th 2反应的交叉调节中的潜在作用进行了讨论。
A cytokine synthesis inhibitory factor (CSIF) is secreted by Th2 clones in response to Con A or antigen stimulation, but is absent in supernatants from Con A-induced Th1 clones. CSIF can inhibit the production of IL-2, IL-3, lymphotoxin (LT)/TNF, IFN-gamma, and granulocyte-macrophage CSF (GM-CSF) by Th1 cells responding to antigen and APC, but Th2 cytokine synthesis is not significantly affected. Transforming growth factor beta (TGF-beta) also inhibits IFN-gamma production, although less effectively than CSIF, whereas IL-2 and IL-4 partially antagonize the activity of CSIF. CSIF inhibition of cytokine synthesis is not complete, since early cytokine synthesis (before 8 h) is not significantly affected, whereas later synthesis is strongly inhibited. In the presence of CSIF, IFN-gamma mRNA levels are reduced slightly at 8, and strongly at 12 h after stimulation. Inhibition of cytokine expression by CSIF is not due to a general reduction in Th1 cell viability, since actin mRNA levels were not reduced, and proliferation of antigen-stimulated cells in response to IL-2, was unaffected. Biochemical characterization, mAbs, and recombinant or purified cytokines showed that CSIF is distinct from IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IFN-gamma, GM-CSF, TGF-beta, TNF, LT, and P40. The potential role of CSIF in crossregulation of Th1 and Th2 responses is discussed.