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

Yates, A. , Stark, J., Klein, N., Antia, R. and Callard, R. (2007) Understanding the slow depletion of memory CD4⁺ T cells in HIV infection. PLoS Medicine, 4(5), e177. (doi: 10.1371/journal.pmed.0040177)

Abstract

<b>Background</b> 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.<p></p> <b>Methods and Findings</b> 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.<p></p> <b>Conclusions</b> 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.<p></p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Yates, Professor Andrew
• Authors: Yates, A., Stark, J., Klein, N., Antia, R., and Callard, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Medicine
• Publisher: Public Library of Science
• ISSN: 1549-1277
• ISSN (Online): 1549-1676
• Copyright Holders: Copyright © 2007 The Authors
• First Published: First published in PLoS Medicine 4(5):e177
• Publisher Policy: Reproduced under a Creative Commons License