Infection of HIV-specific CD4 T helper cells and the clonal composition of the response

JOURNAL OF THEORETICAL BIOLOGY

卷:304

Article

Roy, Sarah M.¹  Wodarz, Dominik¹ 

[1] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Irvine, CA 92697 USA

关键词: Helper T cells;    Mathematical models;    Virus dynamics;    Apparent competition;   

DOI  :  10.1016/j.jtbi.2012.03.015

来源: Elsevier

【 摘 要 】

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. (c) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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