Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada.
Front Immunol. 2019 Sep 6;10:2075. doi: 10.3389/fimmu.2019.02075. eCollection 2019.
Tissue-resident memory T cells (T) are critical to host defense at mucosal tissue sites. However, the parenteral route of immunization as the most commonly used immunization route in practice is not effective in inducing mucosal T cells particularly in the lung. While various respiratory mucosal (RM)-pull strategies are exploited to mobilize parenteral vaccine-primed T cells into the lung, whether such RM-pull strategies can all or differentially induce Ag-specific T cells in the lung remains unclear. Here, we have addressed this issue by using a parenteral TB vaccine-primed and RM-pull model. We show that both Ag-independent and Ag-dependent RM-pull strategies are able to mobilize Ag-specific CD8 T cells into the lung. However, only the RM-pull strategy with cognate antigens can induce robust Ag-specific CD8 T cells in the lung. We also show that the cognate Ag-based RM-pull strategy is the most effective in inducing T cells when carried out during the memory phase, as opposed to the effector phase, of T cell responses to parenteral prime vaccination. We further find that cognate Ag-induced CD4 T cells play an important role in the development of CD8 T cells in the lung. Our study holds implications in developing effective vaccine strategies against respiratory pathogens.
组织驻留记忆 T 细胞(T 细胞)对于黏膜组织部位的宿主防御至关重要。然而,在实践中最常用的免疫接种途径——注射途径,在诱导黏膜 T 细胞方面效果不佳,特别是在肺部。虽然人们利用各种呼吸道黏膜(RM)拉动策略来动员经疫苗接种的外周血 T 细胞进入肺部,但这些 RM 拉动策略是否能全部或有差异地诱导肺部的抗原特异性 T 细胞仍不清楚。在这里,我们通过使用经皮结核疫苗接种和 RM 拉动模型来解决这个问题。我们表明,无论是非抗原依赖性还是抗原依赖性的 RM 拉动策略都能够动员抗原特异性 CD8 T 细胞进入肺部。然而,只有具有同源抗原的 RM 拉动策略才能诱导肺部产生强烈的抗原特异性 CD8 T 细胞。我们还表明,与效应期相比,在针对经皮接种的 T 细胞反应的记忆期进行同源 Ag 基 RM 拉动策略是最有效的诱导 T 细胞的方法。我们进一步发现,同源 Ag 诱导的 CD4 T 细胞在肺部 CD8 T 细胞的发育中发挥重要作用。我们的研究对于开发针对呼吸道病原体的有效疫苗策略具有重要意义。
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