کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4496693 1623906 2012 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Infection of HIV-specific CD4 T helper cells and the clonal composition of the response
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
پیش نمایش صفحه اول مقاله
Infection of HIV-specific CD4 T helper cells and the clonal composition of the response
چکیده انگلیسی

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.


► HIV-specific helper T cells are preferentially infected by HIV.
► We consider a mathematical model between HIV and its target cells.
► No effector responses are taken into account.
► We model two helper cell clones that are not in competition.
► We observe exclusion as well as facilitated persistence of the weaker clone.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Theoretical Biology - Volume 304, 7 July 2012, Pages 143–151
نویسندگان
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