Models of CD8+responses: 1. What is the antigen-independent proliferation program
Models of CD8+responses: 1. What is the antigen-independent proliferation program
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DOI：
10.1006/jtbi.2003.3208
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发表时间：
2003-04-21
影响因子：
2
通讯作者：
Ahmed, R
中科院分区：
文献类型：
--
作者：
Antia, R;Bergstrom, CT;Ahmed, R
最近的实验结果表明，即使用抗原短暂刺激也可以导致抗原特异性CD 8 T细胞经历持续增殖，然后分化成记忆细胞。这些结果表明，这些免疫应答的动态不受抗原水平的持续监测的控制，而是在刺激后免疫细胞致力于“程序”。目前，对控制CD 8细胞增殖和分化的程序知之甚少。例如，我们不知道该程序是否完全由T细胞与抗原的初始接触所指定，或者它是否随后可以通过抗原存在的量进行修改。我们也不知道T细胞增殖和分化的整个程序是否存在于T细胞本身，或者程序的某些组成部分是否由CD 8细胞外部的细胞或分子决定。在本文中，我们构建了简单的数学模型，其中包括抗原非依赖性的增殖和分化的CD 8细胞在急性感染。我们使用这些模型来确定程序必须具有哪些特征，以便与CD 8反应动态的现有数据保持一致，特别是回答上面提出的问题。我们的结果表明，该程序并不完全由T细胞与抗原的首次接触来定义，但可能会在感染后不久的短暂窗口内暴露于抗原而增强;此外，该程序的部分内容可能存在于T细胞外部。最后，我们研究了病原体-宿主共同进化的“程序”的一些后果。(C)2003年由Elsevier Science Ltd.出版
Recent experimental results show that even brief stimulation with antigen can cause antigen-specific CD8 T-cells to undergo sustained proliferation followed by differentiation into memory cells. These results show that the dynamics of these immune responses are not governed by constant monitoring of antigen levels, but rather that following stimulation immune cells commit to a "program". At present relatively little is known about the program which governs CD8 cell proliferation and differentiation. For example, we do not know whether the program is completely specified by the initial encounter of a T cell with antigen, or whether it subsequently can be modified by the amount of antigen present. Nor do we know whether the entire program for T cell proliferation and differentiation resides within the T cell itself, or whether some component(s) of the program are determined by cells or molecules external to the CD8 cell. In this paper we construct simple mathematical models which incorporate antigen-independent proliferation and differentiation of CD8 cells during acute infections. We use these models to determine what characteristics the program must have in order to be consistent with the existing data on the dynamics of CD8 responses, and in particular to answer the questions posed above. Our results suggest that the program is not completely defined by the initial encounter of T cell with antigen but may be augmented by exposure to antigen in a brief window shortly after infection; furthermore, parts of the program may reside external to the T-cells. Finally we examine some of the consequences of the "program" for pathogen-host coevolution. (C) 2003 Published by Elsevier Science Ltd.