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The Journal of Immunology, 202000, 164: 5049-5054.
Copyright © 202000 by The American Association of Immunologists

Quantification of Cell Turnover Kinetics Using 5-Bromo-2'-deoxyuridine1

Sebastian Bonhoeffer*, Hiroshi Mohri{dagger}, David Ho{dagger} and Alan S. Perelson1,*,{ddagger}

* Friedrich Miescher Institute, Basel, Switzerland; {dagger} Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY 10016; and {ddagger} Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545 1 This work was supported by National Institutes of Health Grants RR06555, AI28433 (to A. S. P.), and AI40387 (to D. D. H.). S. B. gratefully acknowledges support from the Novartis Research Foundation. Portions of this work were performed under the auspices of the U.S. Department of Energy.

5-Bromo-2'-deoxyuridine (BrdU) is frequently used to measure the turnover of cell populations in vivo. However, due to a lack of detailed mathematical models that describe the uptake and loss of BrdU in dividing cell populations, assessments of cell turnover kinetics have been largely qualitative rather than quantitative. In this study, we develop a mathematical framework for the analysis of BrdU-labeling experiments. We derive analytical expressions for the fraction of labeled cells within cell populations that are growing, declining, or at equilibrium. Fitting the analytical functions to data allows us to quantify the rates of cell proliferation and cell loss, as well as the rate of cell input from a source. We illustrate this for the BrdU labeling of T lymphocytes of uninfected and SIV-infected rhesus macaques.




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