A primary intestinal helminthic infection rapidly induces a gut-associated elevation of Th2-associated cytokines and IL-3.
A primary intestinal helminthic infection rapidly induces a gut-associated elevation of Th2-associated cytokines and IL-3.
复制标题
DOI：
10.4049/jimmunol.150.8.3434
复制
发表时间：
1993-04
影响因子：
4.4
通讯作者：
A. Svetić;K. Madden;Xia di Zhou;Pin Lu;I. Katona;F. Finkelman;Joseph F. Urban;W. Gause
中科院分区：
文献类型：
--
作者：
A. Svetić;K. Madden;Xia di Zhou;Pin Lu;I. Katona;F. Finkelman;Joseph F. Urban;W. Gause
寄生虫感染的免疫反应特征包括与速发型超敏反应相关的成分：血清IgE升高、嗜酸性粒细胞增多和肠肥大细胞增生。在感染寄生线虫，Heligmosomoides polygyrus，IL-4介导的保护性免疫，表明存在的主机保护性Th 2反应。在这项研究中，我们研究了免疫反应的早期阶段，H。多脑回感染，以确定是否以及在什么阶段出现特定的Th 2样模式。使用定量逆转录-聚合酶链反应分析，我们分析了感染后不同时间点脾脏、肠系膜淋巴结和派伊尔集合淋巴结中IL-2、IFN-γ、IL-3、IL-4、IL-5、IL-6、IL-9和IL-10基因表达的变化。我们的研究结果表明，细胞因子基因表达的高度特异性和可重复性的模式，仍然局限于肠道区域。感染后6 h，Peyer集合淋巴结中IL-5和IL-9 mRNA升高，IL-3在感染后12 ~ 24 h升高。IL-4 RNA在感染后4 - 6天升高，但IFN-γ、IL-2或IL-10 mRNA水平变化不大。感染后IL-3、IL-5和IL-9基因表达的早期增加可能不依赖于T细胞，因为它们在先天性无胸腺小鼠和抗CD 4、抗CD 8 mAb治疗的常规小鼠的派伊尔集合淋巴结中观察到。然而，用这些mAb治疗在感染后6天显著降低细胞因子基因表达，并且在感染后8天，肠系膜淋巴结细胞中增加的IL-4基因表达仅限于CD 4+群体。因此，H.多脑回感染诱导细胞因子基因表达，其限于一些Th 2相关细胞因子，由T非依赖性应答启动，并在T依赖性应答中达到高潮。
The immune response that is characteristic of parasitic helminth infections includes components associated with immediate-type hypersensitivity: elevated serum IgE, eosinophilia, and intestinal mast cell hyperplasia. In infection with the parasitic nematode, Heligmosomoides polygyrus, IL-4 mediates protective immunity, suggesting the presence of a host-protective Th2 response. In this investigation, we examined early stages of immune responsiveness to H. polygyrus infection to determine whether and at what stage a specific Th2-like pattern first appears. Using a quantitative reverse transcriptase-polymerase chain reaction assay, we analyzed changes in IL-2, IFN-gamma, IL-3, IL-4, IL-5, IL-6, IL-9, and IL-10 gene expression in the spleen, mesenteric lymph node, and Peyer's patch at various time points after infection. Our results demonstrate a highly specific and reproducible pattern of cytokine gene expression that remains localized to the enteric region. By 6 h after infection, IL-5 and IL-9 mRNA were elevated in the Peyer's patch and IL-3 was elevated by 12 to 24 h after infection. IL-4 RNA became elevated by 4 to 6 days after infection, but little change was observed in IFN-gamma, IL-2, or IL-10 mRNA levels. The early increases in IL-3, IL-5, and IL-9 gene expression after infection were probably T cell-independent, inasmuch as they were observed in Peyer's patches of congenitally athymic mice and anti-CD4, anti-CD8 mAb-treated conventional mice. However, treatment with these mAb considerably decreased cytokine gene expression 6 days after infection, and 8 days after infection, increased IL-4 gene expression in mesenteric lymph node cells was restricted to the CD4+ population. Thus, H. polygyrus infection induces cytokine gene expression that is restricted to some Th2-associated cytokines, is initiated by a T-independent response, and culminates in a T-dependent response.