Modeling deuterated glucose labeling of T-lymphocytes

Bulletin of Mathematical Biology
Ruy M RibeiroA S Perelson

Abstract

Human immunodeficiency virus type 1 (HIV-1) infects cells of the immune system and leads to depletion of CD4+ T cells, and to an increase of CD8+ T-lymphocytes. However, not much is known about the dynamics of turnover (proliferation and death) of the CD4+ and CD8+ T cell populations in HIV-infected and healthy individuals. A new experimental technique has been developed using deuterated-glucose labeling that provides information on cell turnover in vivo. However, the quantitative interpretation of the data requires the development of specific dynamic models. In this paper we derive two models, a simple one-compartment model and a more complex two-compartment model. These models allow for robust quantification of death and proliferation rates, but careful consideration of the system is necessary to understand what is being measured in each case. We demonstrate that more realistic models can account not only for differences in the turnover rates between HIV-infected and healthy individuals, but also take into consideration the elevated state of activation in HIV infection. The use of these models in the interpretation of the experimental data will increase our knowledge of T cell dynamics in the context of HIV infection.

References

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Citations

Mar 29, 2007·Immunology and Cell Biology·Ruy M Ribeiro
Nov 30, 2007·Bioinformatics·Claus LundegaardMorten Nielsen
Oct 24, 2002·Current Opinion in Hematology·Frances T Hakim, Ronald E Gress
Apr 20, 2012·Journal of the Royal Society, Interface·Rob J De BoerRuy M Ribeiro
May 10, 2003·Proceedings. Biological Sciences·Rob J De BoerAlan S Perelson
Nov 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ruy M RibeiroAlan S Perelson
Jan 15, 2013·Journal of Theoretical Biology·Rob J De Boer, Alan S Perelson
Nov 17, 2009·Journal of Theoretical Biology·R A SergeevI M Rouzine
May 19, 2006·Ecology Letters·Dominik Wodarz
Mar 21, 2007·Immunological Reviews·José A M Borghans, Rob J de Boer
Mar 22, 2002·Nature Reviews. Immunology·Alan S Perelson
Apr 7, 2016·Interface Focus·Mario CastroRuy M Ribeiro
Feb 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rob J De BoerAlan S Perelson
Aug 30, 2019·Current Opinion in Systems Biology·Jessica M Conway, Ruy M Ribeiro
Oct 15, 2021·PLoS Computational Biology·Veronika I ZarnitsynaRustom Antia

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