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PLoS Med. 2007 May;4(5):e177.

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

Author information

1
Department of Biology, Emory University, Atlanta, Georgia, United States of America. ayates2@emory.edu

Erratum in

  • PLoS Med. 2008 Jan;5(1):e11.

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.

PMID:
17518516
PMCID:
PMC1872038
DOI:
10.1371/journal.pmed.0040177
[Indexed for MEDLINE]
Free PMC Article

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