Department of Ecology and Evolutionary Biology, 321 Steinhaus Hall, University of California, Irvine, CA 92697, USA.
J Theor Biol. 2012 Jul 7;304:143-51. doi: 10.1016/j.jtbi.2012.03.015. Epub 2012 Mar 30.
A hallmark of human immunodeficiency virus is its ability to infect CD4+ T helper cells, thus impairing helper cell responses and consequently effector responses whose maintenance depends on help (such as killer T cells and B cells). In particular, the virus has been shown to infect HIV-specific helper cells preferentially. Using mathematical models, we investigate the consequence of this assumption for the basic dynamics between HIV and its target cells, assuming the existence of two independently regulated helper cell clones, directed against different epitopes of the virus. In contrast to previous studies, we examine a relatively simple scenario, only concentrating on the interactions between the virus and its target cells, not taking into account any helper-dependent effector responses. Further, there is no direct competition for space or antigenic stimulation in the model. Yet, a set of interesting outcomes is observed that provide further insights into factors that shape helper cell responses. Despite the absence of competition, a stronger helper cell clone can still exclude a weaker one because the two clones are infected by the same pathogen, an ecological concept called "apparent competition". Moreover, we also observe "facilitation": if one of the helper cell clones is too weak to become established in isolation, the presence of a stronger clone can provide enhanced antigenic stimulation, thus allowing the weaker clone to persist. The dependencies of these outcomes on parameters is explored. Factors that reduce viral infectivity and increase the death rate of infected cells promote coexistence, which is in agreement with the observation that stronger immunity correlates with broader helper cell responses. The basic model is extended to explicitly take into account helper-dependent CTL responses and direct competition. This study sheds further light onto the factors that can influence the clonal composition of HIV-specific helper cell responses, which has implications for the overall pattern of disease progression.
人类免疫缺陷病毒的一个特点是能够感染 CD4+T 辅助细胞，从而损害辅助细胞的反应，进而影响依赖辅助的效应反应（如杀伤 T 细胞和 B 细胞）。特别是，已经表明该病毒优先感染 HIV 特异性辅助细胞。我们使用数学模型，假设存在两个独立调节的辅助细胞克隆，针对病毒的不同表位，来研究这种假设对 HIV 和其靶细胞之间基本动力学的影响。与以前的研究不同，我们研究了一个相对简单的情景，仅集中于病毒与其靶细胞之间的相互作用，而不考虑任何辅助依赖性的效应反应。此外，模型中不存在对空间或抗原刺激的直接竞争。然而，观察到一组有趣的结果，这些结果提供了对影响辅助细胞反应的因素的进一步了解。尽管不存在竞争，但更强的辅助细胞克隆仍然可以排除较弱的克隆，因为两个克隆被同一病原体感染，这是一个称为“明显竞争”的生态学概念。此外，我们还观察到“促进作用”：如果一个辅助细胞克隆太弱而无法单独建立，另一个更强的克隆的存在可以提供增强的抗原刺激，从而使较弱的克隆得以维持。还探讨了这些结果对参数的依赖性。降低病毒感染力和增加感染细胞死亡率的因素促进共存，这与更强的免疫力与更广泛的辅助细胞反应相关的观察结果一致。基本模型被扩展为明确考虑辅助依赖性 CTL 反应和直接竞争。这项研究进一步阐明了影响 HIV 特异性辅助细胞反应的克隆组成的因素，这对疾病进展的总体模式有影响。
