首页> 美国卫生研究院文献>Immunology >Th1/Th2 cell dichotomy in acquired immunity to Bordetella pertussis: variables in the in vivo priming and in vitro cytokine detection techniques affect the classification of T-cell subsets as Th1 Th2 or Th0.
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Th1/Th2 cell dichotomy in acquired immunity to Bordetella pertussis: variables in the in vivo priming and in vitro cytokine detection techniques affect the classification of T-cell subsets as Th1 Th2 or Th0.

机译:Th1 / Th2细胞二分法获得百日咳博德特氏菌的免疫力:体内启动和体外细胞因子检测技术中的变量会影响T细胞亚群的分类如Th1Th2或Th0。

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摘要

In studies of the mechanism of immunity to Bordetella pertussis in a murine respiratory infection model, we have previously demonstrated that natural infection of immunization with a whole cell vaccine induces a potent protective immune response, which is mediated by T-helper type-1 (Th1) cells. In contrast an acellular vaccine generates Th2 cells and is associated with delayed bacterial clearance following respiratory challenge. In the present study we have investigated the apparent Th1/Th2 cell dichotomy in acquired immunity and have examined the factors that affect their induction or detection. The cytokine profiles of B. pertussis-specific T cells in immune animals were determined using antigen-stimulated ex vivo spleen cells or CD4+ T-cell lines and clones established in the presence of interleukin-2 (IL-2) or IL-4. Antigen-specific T cells derived from mice immunized with the acellular vaccine were almost exclusively of the Th2 cell type. In contrast, T-cell lines and clones established following respiratory infection or immunization with the whole cell vaccine were predominantly of the Th1 type. However, a proportion of T cells from convalescent mice, especially when cultured in the presence of IL-4, secreted IL-4 and IL-5 with or without detectable IL-2 and interferon-gamma (IFN-gamma), suggesting that Th0 or Th2 cells were also primed during natural infection in vivo. Furthermore, when mice were assessed 6 months after infection, spleen cells produced significant levels of IL-4 and IL-5, which were not evident at 6 weeks. The route of immunization and the genetic background of the mice were also found to influence the preferential priming of Th1 cells, and this was directly related to the level of protection against respiratory or intracerebral (i.c.) challenge. Our findings underline the critical role of CD4+ Th1 cells in immunity to B. pertussis, but also demonstrate that a number of factors in the in vivo priming and in vitro restimulation can skew the apparent dominance of one Th cell type over another.
机译:在鼠类呼吸道感染模型中对百日咳博德特氏菌免疫的机制研究中,我们先前已证明,用全细胞疫苗免疫自然感染可诱导有效的保护性免疫反应,该反应由T型辅助1型介导(Th1 ) 细胞。相反,无细胞疫苗会产生Th2细胞,并与呼吸刺激后细菌清除延迟有关。在本研究中,我们研究了获得性免疫中明显的Th1 / Th2细胞二分法,并研究了影响其诱导或检测的因素。使用抗原刺激的离体脾细胞或CD4 + T细胞系以及在存在白介素2(IL-2)或IL-4的情况下建立的克隆,确定免疫动物中百日咳博德特氏菌特异性T细胞的细胞因子谱。源自用无细胞疫苗免疫的小鼠的抗原特异性T细胞几乎完全是Th2细胞类型。相反,在呼吸道感染或用全细胞疫苗免疫后建立的T细胞系和克隆主要是Th1型。但是,恢复期小鼠的一部分T细胞,特别是在存在IL-4的情况下培养的T细胞,分泌IL-4和IL-5,有或没有可检测的IL-2和干扰素-γ(IFN-γ),这表明Th0或Th2细胞也在体内自然感染过程中引发。此外,当在感染后6个月对小鼠进行评估时,脾细胞产生了显着水平的IL-4和IL-5,这在6周时不明显。还发现小鼠的免疫途径和遗传背景会影响Th1细胞的优先启动,这直接关系到对呼吸道或脑内(i.c.)攻击的防护水平。我们的发现强调了CD4 + Th1细胞在百日咳博德特氏菌免疫中的关键作用,但同时也表明,体内启动和体外再刺激中的许多因素会使一种Th细胞类型的明显优势偏向另一种。

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