Protection against Helicobacter pylori infection following immunization is IL-12-dependent and mediated by Th1 cells
Protection against Helicobacter pylori infection following immunization is IL-12-dependent and mediated by Th1 cells
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DOI：
10.4049/jimmunol.169.12.6977
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发表时间：
2002-12-15
影响因子：
4.4
通讯作者：
Lycke, N
中科院分区：
文献类型：
--
作者：
Akhiani, AA;Pappo, J;Lycke, N
Th1和Th2细胞在抗螺杆菌感染的免疫保护中的调节作用尚不清楚。在这项研究中，我们报告说，一个主要的H。幽门螺杆菌感染可以在不存在IL-12或IFN-γ的情况下建立。然而，IFN-γ而不是IL-12参与胃炎的发展，因为与IL-12（-/-）或野生型（WT）小鼠相比，IFN-γ（-/-）（GKO）小鼠表现出显著更少的炎症。IL-12（-/-）和GKO小鼠在口服H.幽门螺杆菌裂解物和霍乱毒素佐剂。相比之下，Th2缺陷型、IL-4（-/-）和WT小鼠受到同样良好的保护。在WT小鼠中，在共同施用rIL-12的情况下，粘液素免疫使Ag特异性IFN-γ产生T细胞增加5倍，并使定植细菌减少4倍，证实了Th1细胞在保护中的关键作用。重要的是，只有受保护的IL-4（-/-）和WT小鼠表现出胃粘膜中CD4（+）T细胞的大量流入。与WT小鼠相比，IL-12（-/-）和GKO小鼠的炎症程度大大降低，表明IFN-γ/Th1细胞在免疫后胃炎中也起主要作用。值得注意的是，IL-4（-/-）小鼠的免疫后胃炎明显轻于WT小鼠，尽管具有相似的保护水平，表明免疫保护与胃炎症的程度没有直接联系。只有受保护的小鼠的T细胞产生高水平的IFN-γ来回忆Ag，而受保护和未受保护的小鼠都产生高水平的IL-13。我们的结论是IL-12和Th1反应是至关重要的H。幽门特异性保护性免疫
The regulatory roles of Th1 and Th2 cells in immune protection against Helicobacter infection are not clearly understood. In this study, we report that a primary H. pylori infection can be established in the absence of IL-12 or IFN-gamma. However, IFN-gamma, but not IL-12, was involved in the development of gastritis because IFN-gamma(-/-) (GKO) mice exhibited significantly less inflammation as compared with IL-12(-/-) or wild-type (WT) mice. Both IL-12(-/-) and GKO mice failed to develop protection following oral immunization with H. pylori lysate and cholera toxin adjuvant. By contrast, Th2-deficient, IL-4(-/-), and WT mice were equally well protected. Mucosal immunization in the presence of coadministered rIL-12 in WT mice increased Ag-specific IFN-gamma-producing T cells by 5-fold and gave an additional 4-fold reduction in colonizing bacteria, confirming a key role of Th1 cells in protection. Importantly, only protected IL-4(-/-) and WT mice demonstrated substantial influx of CD4(+) T cells in the gastric mucosa. The extent of inflammation in challenged IL-12(-/-) and GKO mice was much reduced compared with that in WT mice, indicating that IFN-gamma/Th1 cells also play a major role in postimmunization gastritis. Of note, postimmunization gastritis in IL-4(-/-) mice was significantly milder than WT mice, despite a similar level of protection, indicating that immune protection is not directly linked to the degree of gastric inflammation. Only protected mice had T cells that produced high levels of IFN-gamma to recall Ag, whereas both protected and unprotected mice produced high levels of IL-13. We conclude that IL-12 and Th1 responses are crucial for H. pylori-specific protective immunity.