RECOMBINANT INTERLEUKIN-12 SUPPRESSES THE SYNTHESIS OF IMMUNOGLOBULIN-E BY INTERLEUKIN-4 STIMULATED HUMAN-LYMPHOCYTES
RECOMBINANT INTERLEUKIN-12 SUPPRESSES THE SYNTHESIS OF IMMUNOGLOBULIN-E BY INTERLEUKIN-4 STIMULATED HUMAN-LYMPHOCYTES
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DOI：
10.1172/jci115846
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发表时间：
1992-07-01
影响因子：
15.9
通讯作者：
DELESPESSE, G
中科院分区：
文献类型：
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作者：
KINIWA, M;GATELY, M;DELESPESSE, G
Interleukin-12 是最近发现的一种淋巴因子，表现出一系列体外活性，表明在针对病毒等感染因子的保护性免疫中发挥着重要作用。这项研究提供的证据表明 IL-12 也可能与免疫球蛋白同种型的选择有关。我们发现皮摩尔浓度的 rIL-12 显着抑制 IL-4 刺激的 PBMC 合成 IgE。在蛋白质和 mRNA 水平上观察到 IgE 的抑制，它是同种型特异性的，并且可以通过中和抗 IL-12 mAb 来消除。 IL-12 可通过以下方式抑制 IgE 合成：(a) 诱导 IFN-γ（一种已知的 IgE 合成抑制剂）的产生，以及 (b) 通过不依赖于 IFN-γ 的新机制。最好的证据来自对 IL-4 加氢化可的松刺激的脐带血淋巴细胞合成 IgE 的研究，这些淋巴细胞不会产生可检测量的 IFN-γ。在此类培养物中，即使存在大量过量的中和性抗 IFN-γ mAb，rIL-12 也会抑制 IgE 合成。
Interleukin-12 is a recently discovered lymphokine displaying an array of in vitro activities suggesting a major role in protective immunity against infectious agents like viruses. This study provides evidence that IL-12 may also be implicated in the selection of the immunoglobulin isotypes. We show that picomolar concentrations of rIL-12 markedly inhibit the synthesis of IgE by IL-4-stimulated PBMC. The suppression of IgE is observed at the protein and at the mRNA levels, it is isotype specific, and it is abolished by neutralizing anti-IL-12 mAbs. IL-12 may suppress IgE synthesis by: (a) inducing the production of IFN-gamma, a known inhibitor of IgE synthesis and (b) by a novel mechanism which is IFN-gamma independent. The best evidence for this is from studies on IgE synthesis by IL-4-plus hydrocortisone-stimulated umbilical cord blood lymphocytes, which do not produce detectable amounts of IFN-gamma. In such cultures, rIL-12 inhibits IgE synthesis even in the presence of a large excess of neutralizing anti-IFN-gamma mAb.