Modeling deuterated glucose labeling of T-lymphocytes.
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.
Ribeiro
Ruy M
RM
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, MS K710, Los Alamos, New Mexico 87545, USA. ruy@lanl.gov
Mohri
Hiroshi
H
Ho
David D
DD
Perelson
Alan S
AS
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D004279:DNA, Viral / Q000097:blood / Q000378:metabolism; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D015497:HIV-1; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008954:Models, Biological
D004279:DNA, Viral; D003903:Deuterium; D005947:Glucose