Bangs Sarah C, Baban Dilair, Cattan Helen J, Li Chris Ka-Fi, McMichael Andrew J, Xu Xiao-Ning
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
J Immunol. 2009 Feb 15;182(4):1962-71. doi: 10.4049/jimmunol.0802596.
There is much evidence that T cells may be activated via mechanisms that act independently of direct TCR ligation. Despite this, the question of whether such forms of bystander T cell activation occur during immune responses is hotly debated. To address some outstanding questions, we set up an in vitro system within which to analyze bystander T cell activation in human T cells, in the absence of the possibility for TCR cross-reactivity. In addition, we have investigated the genetic, phenotypic, and functional characteristics of bystander-activated T cells. In this study, we show that bystander T cell activation is, indeed, observed during a specific immune response, and that it occurs preferentially among CD4(+) memory T cells. Furthermore, bystander-activated T cells display a distinct gene expression profile. The mechanism for bystander T cell activation involves soluble factors, and the outcome is an elevated level of apoptosis. This may provide an explanation for the attrition of T cell memory pools of heterologous specificity during immune responses to pathogens such as viruses.
有许多证据表明，T细胞可能通过独立于直接TCR连接的机制被激活。尽管如此，在免疫反应期间是否会发生这种形式的旁观者T细胞激活这一问题仍存在激烈争论。为了解决一些悬而未决的问题，我们建立了一个体外系统，用于在不存在TCR交叉反应可能性的情况下分析人T细胞中的旁观者T细胞激活。此外，我们还研究了旁观者激活的T细胞的遗传、表型和功能特征。在本研究中，我们表明在特定免疫反应期间确实观察到了旁观者T细胞激活，并且它优先发生在CD4(+)记忆T细胞中。此外，旁观者激活的T细胞表现出独特的基因表达谱。旁观者T细胞激活的机制涉及可溶性因子，其结果是细胞凋亡水平升高。这可能为在对病毒等病原体的免疫反应期间异源特异性T细胞记忆库的损耗提供一种解释。
