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A mathematical model is developed to characterize the distribution of cell turnover rates within a population of T lymphocytes. Previous models of T-cell dynamics have assumed a constant uniform turnover rate; here we consider turnover in a cell pool subject to clonal proliferation in response to diverse and repeated antigenic stimulation. A basic framework is defined for T-cell proliferation in response to antigen, which explicitly describes the cell cycle during antigenic stimulation and subsequent cell division. The distribution of T-cell turnover rates is then calculated based on the history of random exposures to antigens. This distribution is found to be bimodal, with peaks in cell frequencies in the slow turnover (quiescent) and rapid turnover (activated) states. This distribution can be used to calculate the overall turnover for the cell pool, as well as individual contributions to turnover from quiescent and activated cells. The impact of heterogeneous turnover on the dynamics of CD4(+) T-cell infection by HIV is explored. We show that our model can resolve the paradox of high levels of viral replication occurring while only a small fraction of cells are infected.

Original publication

DOI

10.1006/jtbi.2002.3085

Type

Journal article

Journal

Journal of theoretical biology

Publication Date

11/2002

Volume

219

Pages

177 - 192

Addresses

Department of Infectious Disease Epidemiology, Imperial College of Science, Technology and Medicine, St Mary's Campus, Norfolk Place, Paddington, London W21PG, UK. c.fraser@ic.ac.uk

Keywords

CD4-Positive T-Lymphocytes, Humans, HIV-1, HIV Infections, Recurrence, Antigens, Viral, Lymphocyte Count, Lymphocyte Activation, Virus Replication, Cell Division, Cell Death, Models, Immunological