Document Detail

Modelling deuterium labelling of lymphocytes with temporal and/or kinetic heterogeneity.
MedLine Citation:
PMID:  22513720     Owner:  NLM     Status:  MEDLINE    
To study the kinetics of lymphocytes, models have divided the cell population into subpopulations with different turnover rates. These have been called 'kinetic heterogeneity models' so as to distinguish them from 'temporal heterogeneity models', in which a cell population may have different turnover rates at different times, e.g. when resting versus when activated. We model labelling curves for temporally heterogeneous populations, and predict that they exhibit equal biphasic up- and downslopes. We show when cells divide only once upon activation, these slopes are dominated by the slowest exponent, yielding underestimates of the average turnover rate. When cells undergo more than one division, the labelling curves allow fitting of the two exponential slopes in the temporal heterogeneity model. The same data can also be described with a two-compartment kinetic heterogeneity model. In both instances, the average turnover rate is correctly estimated. Because both models assume a different cell biology but describe the data equally well, the parameters of either model have no simple biological interpretation, as each parameter could reflect a combination of parameters of another biological process. Thus, even if there are sufficient data to reliably estimate all exponentials, one can only accurately estimate an average turnover rate. We illustrate these issues by re-fitting labelling data from healthy and HIV-infected individuals.
Rob J De Boer; Alan S Perelson; Ruy M Ribeiro
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-04-18
Journal Detail:
Title:  Journal of the Royal Society, Interface / the Royal Society     Volume:  9     ISSN:  1742-5662     ISO Abbreviation:  J R Soc Interface     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-07-26     Completed Date:  2012-11-30     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101217269     Medline TA:  J R Soc Interface     Country:  England    
Other Details:
Languages:  eng     Pagination:  2191-200     Citation Subset:  IM    
Department of Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands.
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MeSH Terms
Deuterium / chemistry*
HIV Infections / immunology*
Isotope Labeling
Lymphocytes / immunology*
Models, Immunological*
Grant Support
8R01-OD011095-21/OD/NIH HHS; AI028433/AI/NIAID NIH HHS; P20-RR018754/RR/NCRR NIH HHS; R01 AI028433/AI/NIAID NIH HHS; R01 OD011095/OD/NIH HHS
Reg. No./Substance:

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