Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.
J Immunol. 2009 Dec 15;183(12):7672-81. doi: 10.4049/jimmunol.0902874.
Determining the magnitude and kinetics, together with the phenotypic and functional characteristics of responding CD8 T cells, is critical for understanding the regulation of adaptive immunity as well as in evaluating vaccine candidates. Recent technical advances have allowed tracking of some CD8 T cells responding to infection, and a body of information now exists describing phenotypic changes that occur in CD8 T cells of known Ag-specificity during their activation, expansion, and memory generation in inbred mice. In this study, we demonstrate that Ag but not inflammation-driven changes in expression of CD11a and CD8alpha can be used to distinguish naive from Ag-experienced (effector and memory) CD8 T cells after infection or vaccination. Interestingly and in contrast to inbred mice, tracking polyclonal CD8 T cell responses with this approach after bacterial and viral infections revealed substantial discordance in the magnitude and kinetics of CD8 T cell responses in outbred hosts. These data reveal limitations to the use of inbred mouse strains as preclinical models at vaccine development and suggest the same dose of infection or vaccination can lead to substantial differences in the magnitude and timing of Ag-specific CD8 expansion as well in differences in protective memory CD8 T cell numbers in outbred individuals. This concept has direct relevance to development of vaccines in outbred humans.
确定 CD8 T 细胞应答的幅度和动力学，以及表型和功能特征，对于理解适应性免疫的调节以及评估疫苗候选物至关重要。最近的技术进步使得可以跟踪一些对感染有反应的 CD8 T 细胞，并且现在已经有大量信息描述了在近交系小鼠中，已知 Ag 特异性的 CD8 T 细胞在激活、扩增和记忆生成过程中发生的表型变化。在这项研究中，我们证明，在感染或接种疫苗后，可以使用 Ag 但不是炎症驱动的 CD11a 和 CD8alpha 表达变化来区分幼稚和 Ag 经验（效应和记忆）CD8 T 细胞。有趣的是，与近交系小鼠不同，用这种方法跟踪多克隆 CD8 T 细胞反应后，在杂种宿主中，CD8 T 细胞反应的幅度和动力学存在显著差异。这些数据揭示了在疫苗开发中使用近交系小鼠作为临床前模型的局限性，并表明相同剂量的感染或接种可能导致 Ag 特异性 CD8 扩增的幅度和时间以及保护性记忆 CD8 T 细胞数量的差异在杂种个体中。这个概念与在杂合人群中开发疫苗直接相关。
