Interleukin-4 plays a dominant role in Th1- or Th2-like responses during the primary immune response to the hapten penicillin
Interleukin-4 plays a dominant role in Th1- or Th2-like responses during the primary immune response to the hapten penicillin
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DOI：
10.1016/0161-5890(95)00119-0
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发表时间：
1996-01-01
影响因子：
3.6
通讯作者：
Pallardy, M
中科院分区：
文献类型：
--
作者：
Kerdine, S;Lebrec, H;Pallardy, M
尽管在对病原体或蛋白抗原的免疫应答期间对Th 1/Th 2平衡进行了大量研究，但关于在单次注射半抗原化合物后调节Th 1/Th 2分化的早期事件知之甚少。在这项工作中，我们研究了具有不同MHC单倍型的两种小鼠品系SJL（H-2（s））和Balb/c（H-2（d））如何对皮下注射的苄青霉素偶联破伤风环（BPO-TT）产生不同的初次免疫应答。SJL小鼠显示出较高的BPO特异性IgG 1应答，在第10天达到最大值，无BPO特异性IgG 2a应答。与此相反，Balb/c小鼠在第15天和第22天显示出高BPO特异性IgG 2a应答和弱IgG 1产生。在SJL小鼠中，对BPO-TT的反应的特征在于非常早期和高的IL-4 mRNA表达。在Balb/c中，观察到IL-4 mRNA的延迟和较弱的表达。IL-2和IFN-γ mRNA表达的动力学在两种菌株中相当，但IFN-γ mRNA表达在SJL中高于Balb/c。IL-4的体内中和在SJL小鼠中诱导显著的BPO特异性IgG 2a产生和IgG 1产生的两倍减少，而其在Balb/c小鼠中加速BPO特异性IgG 2a的产生。此外，BPO-TT免疫后IL-12 p40和IL-10 mRNA表达的研究显示，Balb/c小鼠中IL-12 p40 mRNA表达更高，SJL中IL-10 mRNA表达略高。两者合计，我们的数据表明，Th 1或Th 2分化的半抗原化合物，如青霉素的初级免疫反应可能是由动力学和IL-4的生产水平，而不是由IFN-γ的水平。其他细胞因子如IL-10和IL-12可能有助于调节这种反应。
Despite a large number of studies on the Th1/Th2 balance during immune response to pathogens or protein antigens, little is known concerning the early events which regulate Th1/Th2 differentiation following a single injection of haptenic compounds. In this work, we studied how two mouse strains with different MHC haplotypes, SJL (H-2(s)) and Balb/c (H-2(d)), could develop different primary immune responses to subcutaneously injected benzylpenicillin coupled to tetanus toroid (BPO-TT). The SJL mice showed a high BPO-specific IgG1 response that was maximum on day 10 and no BPO-specific IgG2a response. In contrast, Balb/c mice showed a high BPO-specific IgG2a response on days 15 and 22 and a weak IgG1 production. In SJL mice, the response to BPO-TT was characterized by a very early and high IL-4 mRNA expression. In Balb/c, a delayed and weaker expression of IL-4 mRNA was observed. Kinetics of IL-2 and IFN-gamma mRNA expression were comparable in both strains, but IFN-gamma mRNA expression was higher in SJL than in Balb/c. In vivo neutralization of IL-4 induced a significant BPO-specific IgG2a production and a two-fold reduction of IgG1 production in SJL mice while it accelerated production of BPO-specific IgG2a in Balb/c mice. In addition, studies of IL-12 p40 and IL-10 mRNA expression following immunization with BPO-TT showed a greater IL-12 p40 mRNA expression in Balb/c mice and a slightly higher IL-10 mRNA expression in SJL. Taken together, our data suggest that Th1 or Th2 differentiation in primary immune responses to haptenic compounds such as penicillin may be driven by the kinetics and the level of IL-4 production rather than by the level of IFN-gamma. Additional cytokines such as IL-10 and IL-12 are likely to contribute to the regulation of this response.