Barnard A, Mahon B P, Watkins J, Redhead K, Mills K H
Department of Biology, St Patrick's College, Maynooth, Co. Kildare, Ireland.
Immunology. 1996 Mar;87(3):372-80. doi: 10.1046/j.1365-2567.1996.497560.x.
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.
在鼠类呼吸道感染模型中对百日咳博德特氏菌免疫机制的研究中，我们之前已经证明，用全细胞疫苗进行自然感染或免疫接种可诱导产生强大的保护性免疫反应，该反应由1型辅助性T细胞（Th1）介导。相比之下，无细胞疫苗会产生Th2细胞，并且与呼吸道攻击后细菌清除延迟有关。在本研究中，我们调查了获得性免疫中明显的Th1/Th2细胞二分法，并研究了影响它们诱导或检测的因素。使用抗原刺激的体外脾细胞或在白细胞介素-2（IL-2）或IL-4存在下建立的CD4+ T细胞系和克隆来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。用无细胞疫苗免疫的小鼠来源的抗原特异性T细胞几乎完全是Th2细胞类型。相比之下，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类型。然而，恢复期小鼠的一部分T细胞，特别是在IL-4存在下培养时，无论是否可检测到IL-2和干扰素-γ（IFN-γ），都会分泌IL-4和IL-5，这表明在体内自然感染过程中也启动了Th0或Th2细胞。此外，当在感染后6个月对小鼠进行评估时，脾细胞产生了显著水平的IL-4和IL-5，而在6周时并不明显。还发现免疫途径和小鼠的遗传背景会影响Th1细胞的优先启动，这与针对呼吸道或脑内（i.c.）攻击的保护水平直接相关。我们的研究结果强调了CD4+ Th1细胞在百日咳博德特氏菌免疫中的关键作用，但也表明体内启动和体外再刺激中的一些因素会使一种Th细胞类型相对于另一种的明显优势发生偏差。
