Recombinant interferon-alpha selectively inhibits the production interleukin-5 by human CD4(+) T cells
Recombinant interferon-alpha selectively inhibits the production interleukin-5 by human CD4(+) T cells
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DOI：
10.1172/jci118417
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发表时间：
1996-01-15
影响因子：
15.9
通讯作者：
Goldman, M
中科院分区：
文献类型：
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作者：
Schandene, L;DelPrete, GF;Goldman, M
用PMA和抗CD28单抗联合或抗CD3单抗刺激B7-1/CD32转染的小鼠成纤维细胞，首先分析重组干扰素-α对人CD4(+)T细胞产生IL-5的影响。我们发现，通过静息CD4(+)T细胞，干扰素-α以剂量依赖的方式深刻地抑制IL-5的产生，而IL-10在两个系统中都被上调。在PMA和抗CD28单抗中加入中和的抗IL-10单抗，可通过静息CD4(+)T细胞上调IL-5的产生，但不能阻止干扰素-α对IL-5的抑制作用。然后，我们分析了干扰素-α对从两名高嗜酸性粒细胞综合征患者外周血中分离的分化的2型辅助细胞(Th2)CD4(+)CD3(-)细胞产生细胞因子的影响。在这两种情况下，干扰素-α显著抑制IL-5的产生，而诱导IL-4和IL-10轻度上调。最后，在一组体外产生的Th2和Th0克隆上证实了干扰素-α对IL-5产生的抑制作用。在6个克隆中，有2个克隆的IL-5抑制与IL-4和IL-10的上调有关，我们认为干扰素-α选择性地下调人CD4(+)T细胞合成IL-5。
The effects of recombinant IFN-alpha on the production of IL-5 by human CD4(+) T cells were first analyzed on resting CD4(+) T cells purified from normal PBMC and stimulated either with a combination of PMA and anti-CD28 mAb or anti-CD3 mAb cross-linked on B7-1/CD32-transfected mouse fibroblasts. We found that IFN-alpha profoundly inhibited in a dose-dependent manner IL-5 production by resting CD4(+) T cells whereas IL-10 was upregulated in both systems. The addition of a neutralizing anti-IL-10 mAb to PMA and anti-CD28 mAb upregulated IL-5 production by resting CD4(+) T cells but did not prevent IFN-alpha-induced IL-5 inhibition. We then analyzed the effect of IFN-alpha on the production of cytokines by differentiated type 2 helper (Th2) CD4(+)CD3(-) cells isolated from peripheral blood of two patients with the hypereosinophilic syndrome. In both cases, IFN-alpha markedly inhibited IL-5 production while it induced mild upregulation of IL-4 and IL-10. Finally, the inhibitory effect of IFN-alpha on IL-5 production was confirmed on a panel of Th2 and Th0 clones generated in vitro. In 2 out of 6 clones, IL-5 inhibition was associated with upregulation of IL-4 and IL-10, We conclude that IFN-alpha selectively downregulates IL-5 synthesis by human CD4(+) T cells.