T cell state transition produces an emergent change detector.
T cell state transition produces an emergent change detector.
复制标题
DOI：
10.1016/j.jtbi.2011.01.031
复制
发表时间：
2011-04-21
影响因子：
2
通讯作者：
Lee, Peter P.
中科院分区：
文献类型：
--
作者：
Kim, Peter S.;Lee, Peter P.
关键词：
我们使用一个常微分方程系统来模拟从初始激活到T细胞扩张和收缩的T细胞反应的各个阶段。这种建模的结果表明，状态转换使T细胞群能够检测变化并有效地响应抗原刺激水平的变化，而不仅仅是抗原的存在或不存在。产生这种紧急变化检测器的系统的一个关键组成部分是初始T细胞的初始激活。激活步骤创建了一个屏障，将幼稚T细胞的长期缓慢动态与效应T细胞的短期快速动态分开。这种分离允许T细胞群体将抗原水平的当前最新变化与长期稳态水平进行比较。因此，T细胞群非常有效地响应抗原水平的突然变化，即使抗原在变化之前已经存在。这一特征为T细胞提供了一种机制，使其对快速扩展的抗原刺激源（如病毒）做出反应，同时保持对恒定或缓慢波动的刺激源（如生长期间的健康组织）的耐受性。除了对T细胞活化进行建模之外，我们还制定了效应T细胞增殖的模型，该模型响应于在整个T细胞应答中分泌的阳性生长信号的消耗。我们讨论了T细胞和生长信号之间的相互作用如何产生一个紧急阈值检测器，优先响应抗原刺激的大变化，而忽略小的。作为最后一步，我们讨论了如何从头生成的适应性调节性T细胞在T细胞反应的后期创建一个负反馈回路，控制T细胞反应的持续时间和幅度。因此，免疫网络不断调整（自身和非自身）抗原的基线变化，并主要对这些抗原的突然变化做出反应，而不仅仅是它们的存在或不存在。
We model the stages of a T cell response from initial activation to T cell expansion and contraction using a system of ordinary differential equations. Results of this modeling suggest that state transitions enable the T cell population to detect change and respond effectively to changes in antigen stimulation levels, rather than simply the presence or absence of antigen. A key component of the system that gives rise to this emergent change detector is initial activation of naïve T cells. The activation step creates a barrier that separates the long-term, slow dynamics of naïve T cells from the short-term, fast dynamics of effector T cells. This separation allows the T cell population to compare current, up-to-date changes in antigen levels to long-term, steady state levels. As a result, the T cell population responds very effectively to sudden shifts in antigen levels, even if the antigen were already present prior to the change. This feature provides a mechanism for T cells to react to rapidly expanding sources of antigen stimulation, such as viruses, while maintaining tolerance to constant or slowly fluctuating sources of stimulation, such as healthy tissue during growth. In addition to modeling T cell activation, we also formulate a model of the proliferation of effector T cells in response to the consumption of positive growth signal, secreted throughout the T cell response. We discuss how the interaction between T cells and growth signal generates an emergent threshold detector that responds preferentially to large changes in antigen stimulation while ignoring small ones. As a final step, we discuss how the de novo generation of adaptive regulatory T cells during the latter phase of the T cell response creates a negative feedback loop that controls the duration and magnitude of the T cell response. Hence, the immune network continually adjusts to a shifting baseline of (self and non-self) antigens, and responds primarily to abrupt changes in these antigens rather than merely their presence or absence.
登录
查看更多内容
影响因子：
4.3
作者：
Rong L;Perelson AS
通讯作者：
Perelson AS
影响因子：
1.9
作者：
Kirschner, D;Panetta, JC
通讯作者：
Panetta, JC
影响因子：
2
作者：
Chao, DL;Davenport, MP;Perelson, AS
通讯作者：
Perelson, AS
影响因子：
2
作者：
León, K;Peréz, R;Carneiro, J
通讯作者：
Carneiro, J
DOI：
10.1084/jem.143.6.1391
发表时间：
1976-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cantor H;Shen FW;Boyse EA
通讯作者：
Boyse EA