Quantitative analysis of the CD8+ T-cell response to readily eliminated and persistent viruses.
Quantitative analysis of the CD8+ T-cell response to readily eliminated and persistent viruses.
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DOI：
10.1098/rstb.2000.0647
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发表时间：
2000-08
期刊：
影响因子：
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通讯作者：
Peter C. Doherty;J. Riberdy;Gabrielle T. Belz
中科院分区：
文献类型：
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作者：
Peter C. Doherty;J. Riberdy;Gabrielle T. Belz
肽特异性CD8+ T细胞直接染色技术的最新发展彻底改变了病毒感染中细胞介导免疫（CMI）的分析。该方法已被用于量化用容易消除的甲型流感病毒（fluA）和持久性γ疱疹病毒（gammaHV）感染实验室小鼠的急性和长期后果。现在，这是第一次，可能的工作与真实的数字在CD8+ T CMI的分析，并确定各种特性的响应淋巴细胞通过直接流式细胞术分析和通过分选进一步在体外操作。虽然我们正在迅速积累大量的数字数据，但在后一方面所做的工作相对较少。流感病毒A和γ HV特异性应答的急性、抗原驱动阶段看起来相当相似，但在持续性感染中，CD8+ T细胞数量长期维持在较高的“设定点”。类似地，这些“记忆”T细胞在感染γ HV的小鼠中继续以更高的速度分裂。在两个实验系统中，二次激发后的回忆反应的性质也产生了新的见解，并且已经确定了大量病毒特异性CD8+ T细胞所赋予的保护程度。然而，仍有许多参数很少受到关注，部分原因是它们难以衡量。这些包括抗原特异性CD8+ T细胞损失的速率，淋巴细胞“散居”到其他组织的程度，以及功能特征的多样性，周转率，克隆寿命和再循环概况。免疫学家的基本问题仍然是我们如何协调免疫系统的非凡可塑性与维持稳定环境的机制。这种在易于操作的小鼠模型中量化CD8+ T细胞反应的新能力具有明显的阐明稳态控制的潜力，特别是如果在适当的预测模型的背景下设计该问题的实验方法。
The recent development of techniques for the direct staining of peptide-specific CD8+ T cells has revolutionized the analysis of cell-mediated immunity (CMI) in virus infections. This approach has been used to quantify the acute and long-term consequences of infecting laboratory mice with the readily eliminated influenza A viruses (fluA) and a persistent gammaherpesvirus (gammaHV). It is now, for the first time, possible to work with real numbers in the analysis of CD8+ T CMI, and to define various characteristics of the responding lymphocytes both by direct flow cytometric analysis and by sorting for further in vitro manipulation. Relatively little has yet been done from the latter aspect, though we are rapidly accumulating a mass of numerical data. The acute, antigen-driven phases of the fluA and gammaHV-specific response look rather similar, but CD8+ T-cell numbers are maintained in the long term at a higher 'set point' in the persistent infection. Similarly, these 'memory' T cells continue to divide at a much greater rate in the gammaHV-infected mice. New insights have also been generated on the nature of the recall response following secondary challenge in both experimental systems, and the extent of protection conferred by large numbers of virus-specific CD8+ T cells has been determined. However, there are still many parameters that have received little attention, partly because they are difficult to measure. These include the rate of antigen-specific CD8+ T-cell loss, the extent of the lymphocyte 'diaspora' to other tissues, and the diversity of functional characteristics, turnover rates, clonal life spans and recirculation profiles. The basic question for immunologists remains how we reconcile the extraordinary plasticity of the immune system with the mechanisms that maintain a stable milieu interieur. This new capacity to quantify CD8+ T-cell responses in readily manipulated mouse models has obvious potential for illuminating homeostatic control, particularly if the experimental approaches to the problem are designed in the context of appropriate predictive models.