Allan Martin J, Callard Robin, Stark Jaroslav, Yates Andrew
Institute of Child Health, University College London, UK.
J Theor Biol. 2004 May 7;228(1):81-95. doi: 10.1016/j.jtbi.2003.12.008.
Key features of the kinetics of T lymphocyte proliferative responses are remarkably insensitive to the nature of the antigenic stimulus. This consistency suggests the presence of an antigen-independent mechanism regulating T cell clonal expansion. Knowledge of such a mechanism could allow us to modulate T helper cell (CD4+) and cytotoxic T cell (CD8+) responses more effectively. Using a simple mathematical model of T cell proliferation and death, we investigate a variety of plausible mechanisms and compare the model predictions to experimental data from the literature. We find that irrespective of the details of the mechanism, rates of apoptosis must progressively increase to control a T cell response. If apoptosis is mediated by cell-cell contact this alone is sufficient to regulate both (CD4+) and (CD8+) T cell responses. Proliferation of both T cell subsets can also be regulated by an internal programme, by cytokine signalling, or by an APC-mediated route. To regulate (CD8+) T cells these mechanisms must change both apoptosis and division rates, and this change must occur with time not division number.
T淋巴细胞增殖反应动力学的关键特征对抗抗原刺激的性质极为不敏感。这种一致性表明存在一种调节T细胞克隆扩增的抗原非依赖性机制。了解这种机制可以使我们更有效地调节辅助性T细胞（CD4 +）和细胞毒性T细胞（CD8 +）的反应。使用T细胞增殖和死亡的简单数学模型，我们研究了各种合理的机制，并将模型预测与文献中的实验数据进行比较。我们发现，无论机制的细节如何，细胞凋亡率都必须逐渐增加以控制T细胞反应。如果细胞凋亡是由细胞间接触介导的，那么仅此一点就足以调节（CD4 +）和（CD8 +）T细胞反应。两个T细胞亚群的增殖也可以通过内部程序、细胞因子信号传导或APC介导的途径来调节。为了调节（CD8 +）T细胞，这些机制必须同时改变细胞凋亡率和分裂率，并且这种改变必须随时间而不是分裂次数发生。
