Mathematical Modeling of Cell Population Dynamics

我们正在开发T细胞分化和稳态机制的数学和计算模型。在健康个体中，细胞死亡、增殖和分化为具有一定效应功能和增殖潜力的T细胞亚型之间的平衡维持了足够的循环和外周效应细胞群。在HIV / SIV感染的个体/恒河猴中，淋巴系统的损伤和初始病毒对周围T细胞（尤其是粘膜组织中的T细胞）的杀伤，会导致周围效应细胞的立即缺失，即使在使用抗逆转录病毒药物治疗后，这种缺陷仍然存在，因为中央（再循环）T细胞的恢复能力被破坏。

We are developing mathematical and computational models of mechanisms of T cell differentiation and homeostasis. In healthy individuals, a balance between cell death, proliferation and differentiation into T cell subtypes with certain effector functions and proliferative potential maintains a sufficient population of recirculating and peripheral effector cells. In HIV / SIV infected individuals / Rhesus macaques, damage to the lymphoid system and the initial viral killing of peripheral T cells especially in the mucosal tissues lead to an immediate deficit of effector cells in the periphery which persists even after treatment with anti-retroviral drugs because the restorative capacity of the central (recirculating) T cells is destroyed. We are trying to answer the following questions: What leads to a destabilization of T cell proliferation and differentiation in HIV / SIV infection? How does this manifest itself as altered proliferation/death/differentiation rates of T cells? What are the differences between CD4 and CD8 cells? To try to answer these questions we develop mathematical models describing the division, death and differentiation of T cells. These models can be represented as sets of coupled linear ordinary differential equations for the dynamics of the sizes of the different cell populations. We then try to determine which model is capable of most precisely matching the experimental data through parameter optimizations (fitting).