抗原竞争动力学在调节免疫应答中的作用
The role of antigen-competitive dynamics in regulating the immune response
摘要：
T细胞在感染期间的克隆扩增受到严格调控，以确保针对入侵病原体的适当免疫应答。虽然实验已经绘制了从膨胀到收缩的轨迹，但控制这种反应的机制之间的相互作用尚未完全理解。基于实验数据，我们提出了一个模型，其中CD4+ T细胞扩增的动力学是通过T细胞和抗原呈递细胞之间的相互作用来控制的，其中T细胞刺激与抗原可用性成正比，抗原可用性通过T细胞下调抗原来调节。这种抗原依赖性反馈机制与细胞增殖速率的内在降低一起起作用，这也可能是减缓扩增的原因。我们的模型可以成功地预测T细胞招募率到分裂，扩增和克隆爆发大小每个细胞时，初始前体是不同的，或者当T细胞被引入到一个正在进行的免疫反应后期。重要的是，研究结果表明，T细胞和抗原呈递细胞之间的反馈机制，以及细胞增殖速率的降低，可以解释免疫系统适应初始条件变化或随后发生的变化的能力。
英文摘要：
The clonal expansion of T cells during an infection is tightly regulated to ensure an appropriate immune response against invading pathogens. Although experiments have mapped the trajectory from expansion to contraction, the interplay between mechanisms that control this response are not fully understood. Based on experimental data, we propose a model in which the dynamics of CD4+ T cell expansion is controlled through the interactions between T cells and antigen-presenting cells, where T cell stimulation is proportional to antigen availability and antigen availability is regulated through downregulation of antigen by T cells. This antigen-dependent-feedback mechanism operates alongside an intrinsic reduction in cell proliferation rate that may also be responsible for slowing expansion. Our model can successfully predict T cell recruitment rates into division, expansion and clonal burst size per cell when initial precursors are varied or when T cells are introduced late into an ongoing immune response. Importantly, the findings demonstrate that a feedback mechanism between T cells and antigen presenting cells, along with a reduction in cell proliferation rate, can explain the ability of the immune system to adapt its response to variations in initial conditions or changes that occur later in the response, ensuring a robust yet controlled line of defence against pathogens.
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