Swinton J, Schweitzer A N, Anderson R M
Wellcome Research Centre for Parasitic Infections, Imperial College, London, U.K.
J Theor Biol. 1994 Jul 7;169(1):23-30. doi: 10.1006/jtbi.1994.1127.
Much work on the induction of non-responsiveness in lymphocytes suggests that it takes two signals to activate a cell correctly, and that receipt of the first signal alone not only causes suboptimal response, but also subsequent non-responsiveness or anergy. This paper discusses not anergy, but the original suboptimal response in the context of the well known but poorly understood phenomenon of high zone tolerance in experiments studying immunological responses to a range of antigen concentrations (low to high "zones"). We proceed to ask specific questions about the nature and timing of the signals involved. We construct three different models describing how the second signal might be received and use them to predict the shapes of dose-response curves. Comparison with data enables us to select, from a dynamical perspective, the most likely mechanism and to tentatively exclude a number of proposed mechanisms for high zone tolerance. We suggest that the stage at which a cell becomes susceptible to anergy is crucial and that it is over-contact, rather than lack of contact, which is important in the induction of tolerance.
许多关于淋巴细胞无反应性诱导的研究表明，正确激活一个细胞需要两个信号，仅接收第一个信号不仅会导致反应欠佳，还会导致随后的无反应性或失能。本文讨论的不是失能，而是在研究对一系列抗原浓度（从低到高“区域”）的免疫反应的实验中，在众所周知但了解甚少的高区耐受现象背景下的最初反应欠佳情况。我们进而提出有关所涉及信号的性质和时间的具体问题。我们构建了三种不同的模型来描述第二个信号可能如何被接收，并使用它们来预测剂量反应曲线的形状。与数据的比较使我们能够从动力学角度选择最可能的机制，并初步排除一些提出的高区耐受机制。我们认为，细胞变得易患失能的阶段至关重要，并且在耐受诱导中起重要作用的是过度接触，而非接触不足。
