Department of Mathematics, New Jersey City University, Jersey City, NJ 07305-1597, USA.
Bull Math Biol. 2010 Jul;72(5):1208-53. doi: 10.1007/s11538-009-9488-5. Epub 2010 Feb 12.
A mathematical model of the host's immune response to HIV infection is proposed. The model represents the dynamics of 13 subsets of T cells (HIV-specific and nonspecific, healthy and infected, T4 and T8 cells), infected macrophages, neutralizing antibodies, and virus. The results of simulation are in agreement with published data regarding T4 cell concentration and viral load, and exhibit the typical features of HIV infection, i.e. double viral peaks in the acute stage, sero conversion, inverted T cell ratio, establishment of set points, steady state, and decline into AIDS. This result is achieved by taking into account thymic aging, viral and infected cell stimulation of specific immune cells, background nonspecific antigens, infected cell proliferation, viral production by infected macrophages and T cells, tropism, viral, and immune adaptation. Starting from this paradigm, changes in the parameter values simulate observed differences in individual outcomes, and predict different scenarios, which can suggest new directions in therapy. In particular, large parameter changes highlight the potentially critical role of both very vigorous and extremely damped specific immune response, and of the elimination of virus release by macrophages. Finally, the time courses of virus, antibody and T cells production and removal are systematically investigated, and a comparison of T4 and T8 cell dynamics in a healthy and in a HIV infected host is offered.
提出了一个描述宿主对 HIV 感染的免疫反应的数学模型。该模型描述了 13 种 T 细胞亚群（HIV 特异性和非特异性、健康和感染、T4 和 T8 细胞）、感染的巨噬细胞、中和抗体和病毒的动态变化。模拟结果与关于 T4 细胞浓度和病毒载量的已发表数据一致，并表现出 HIV 感染的典型特征，即在急性阶段出现双重病毒峰值、血清转换、倒置的 T 细胞比值、设定点建立、稳态和发展为艾滋病。通过考虑胸腺衰老、特异性免疫细胞的病毒和感染细胞刺激、背景非特异性抗原、感染细胞增殖、感染的巨噬细胞和 T 细胞的病毒产生、嗜性、病毒和免疫适应，实现了这一结果。从这个范例出发，通过改变参数值来模拟个体结果的观察到的差异，并预测不同的情况，这可以为治疗提供新的方向。特别是，参数的大幅变化突出了非常强烈和极度减弱的特异性免疫反应以及巨噬细胞消除病毒释放的潜在关键作用。最后，系统地研究了病毒、抗体和 T 细胞产生和清除的时间过程，并提供了健康宿主和 HIV 感染宿主中 T4 和 T8 细胞动力学的比较。
