Models

Dataset Information

116

Yates2007_TcellHomeostasisProliferation


ABSTRACT: This a model from the article: Understanding the slow depletion of memory CD4+ T cells in HIV infection. Yates A, Stark J, Klein N, Antia R, Callard R. PLoS Med. 2007;4(5):e177. 17518516 , Abstract: BACKGROUND: The asymptomatic phase of HIV infection is characterised by a slow decline of peripheral blood CD4(+) T cells. Why this decline is slow is not understood. One potential explanation is that the low average rate of homeostatic proliferation or immune activation dictates the pace of a "runaway" decline of memory CD4(+) T cells, in which activation drives infection, higher viral loads, more recruitment of cells into an activated state, and further infection events. We explore this hypothesis using mathematical models. METHODS AND FINDINGS: Using simple mathematical models of the dynamics of T cell homeostasis and proliferation, we find that this mechanism fails to explain the time scale of CD4(+) memory T cell loss. Instead it predicts the rapid attainment of a stable set point, so other mechanisms must be invoked to explain the slow decline in CD4(+) cells. CONCLUSIONS: A runaway cycle in which elevated CD4(+) T cell activation and proliferation drive HIV production and vice versa cannot explain the pace of depletion during chronic HIV infection. We summarize some alternative mechanisms by which the CD4(+) memory T cell homeostatic set point might slowly diminish. While none are mutually exclusive, the phenomenon of viral rebound, in which interruption of antiretroviral therapy causes a rapid return to pretreatment viral load and T cell counts, supports the model of virus adaptation as a major force driving depletion. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Yates A, Stark J, Klein N, Antia R, Callard R. (2007) - version03 The original CellML model was created by: Lloyd, Catherine, May c.lloyd@aukland.ac.nz The University of Auckland The Bioengineering Institute This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

SUBMITTER: Vijayalakshmi Chelliah  

PROVIDER: MODEL4028801312 | BioModels | 2005-01-01

REPOSITORIES: BioModels

altmetric image

Publications

Understanding the slow depletion of memory CD4+ T cells in HIV infection.

Yates Andrew A   Stark Jaroslav J   Klein Nigel N   Antia Rustom R   Callard Robin R  

PLoS medicine 20070501 5


The asymptomatic phase of HIV infection is characterised by a slow decline of peripheral blood CD4(+) T cells. Why this decline is slow is not understood. One potential explanation is that the low average rate of homeostatic proliferation or immune activation dictates the pace of a "runaway" decline of memory CD4(+) T cells, in which activation drives infection, higher viral loads, more recruitment of cells into an activated state, and further infection events. We explore this hypothesis using m  ...[more]

Similar Datasets

1000-01-01 | S-EPMC1872038 | BioStudies
1000-01-01 | S-EPMC4692447 | BioStudies
1000-01-01 | S-EPMC2662887 | BioStudies
1000-01-01 | S-EPMC6053365 | BioStudies
2006-01-01 | S-EPMC1459071 | BioStudies
1000-01-01 | S-EPMC4761827 | BioStudies
1000-01-01 | S-EPMC2643790 | BioStudies
2014-01-01 | S-EPMC4148445 | BioStudies
1000-01-01 | S-EPMC2596741 | BioStudies
1000-01-01 | S-EPMC2546913 | BioStudies