Negative feedback mechanism suppresses interleukin-12 production by antigen-presenting cells interacting with T helper 2 cells

Negative feedback mechanism suppresses interleukin-12 production by antigen-presenting cells interacting with T helper 2 cells
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DOI:
10.1002/eji.1830260318
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发表时间:
1996-03-01
影响因子:
5.4
通讯作者:
Nariuchi, H
Nariuchi, H
中科院分区:
医学3区
文献类型:
--
作者:
Hino, A;Nariuchi, H

文献摘要

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白细胞介素12(IL-12)是由单核细胞通过CD40结扎产生的。在本实验中,小鼠脾抗原提呈细胞(APC)通过CD40-CD40配体(CD40L)与辅助性T细胞(Th1)1克隆相互作用而产生IL-12,但不与Th2克隆相互作用。外源性IL-10可抑制Th1克隆相互作用所诱导的IL-12的产生。Th2克隆产生足够数量的IL-10以抑制Th1克隆诱导的IL-12的产生。在抗IL-10单抗存在下,脾APC与Th2克隆相互作用产生IL-12。这些结果表明,抗原刺激的Th2细胞产生的IL-10抑制了APC与Th2细胞相互作用产生的IL-12。IL-12由p35和p40两个亚基组成。在我们的实验中,IL-10对p40基因表达的影响比对p35基因表达的影响更大,这表明IL-10主要通过影响p40基因表达来调节APC产生IL-12。
Interleukin-12 (IL-12) has been shown to be produced by monocytes by the ligation of CD40. In the present experiments, IL-12 is shown to be produced by murine spleen antigen-presenting cells (APC) by interaction with T helper 1 (Th1) 1 clones through CD40-CD40 ligand (CD40L) interaction, but not with Th2 clones. The IL-12 production induced by the Th1 clone interaction was inhibited by the addition of exogenous IL-10. Th2 clones were shown to produce a sufficient amount of IL-10 to inhibit the IL-12 production induced by Th1 clones. In the presence of anti-IL-10 monoclonal antibodies splenic APC interacting with Th2 clones produced IL-12. These results indicate that IL-10 produced by Th2 cells stimulated with antigen suppress IL-12 production of APC interacting with Th2 cells. IL-12 is composed of two subunits, p35 and p40. In our experiments, p40 mRNA accumulation was shown to be affected by IL-10 more severely than the accumulation of p35 mRNA, indicating that IL-10 regulates IL-12 production by APC mainly by affecting p40 mRNA accumulation.