title: Estimating lymphocyte division and death rates from CFSE data.
abstract: The division tracking dye, carboxyfluorescin diacetate succinimidyl ester (CFSE) is currently the most informative labeling technique for characterizing the division history of cells in the immune system. Gett and Hodgkin [Nat. Immunol. 1:239-244, 2000] have pioneered the quantitative analysis of CFSE data. We confirm and extend their data analysis approach using simple mathematical models. We employ the extended Gett and Hodgkin [Nat. Immunol. 1:239-244, 2000] method to estimate the time to first division, the fraction of cells recruited into division, the cell cycle time, and the average death rate from CFSE data on T cells stimulated under different concentrations of IL-2. The same data is also fitted with a simple mathematical model that we derived by reformulating the numerical model of Deenick et al. [J. Immunol. 170:4963-4972, 2003]. By a non-linear fitting procedure we estimate parameter values and confidence intervals to identify the parameters that are influenced by the IL-2 concentration. We obtain a significantly better fit to the data when we assume that the T cell death rate depends on the number of divisions cells have completed. We provide an outlook on future work that involves extending the Deenick et al. [J. Immunol. 170:4963-4972, 2003] model into the classical smith-martin model, and into a model with arbitrary probability distributions for death and division through subsequent divisions.
authors.affiliation: Theoretical Biology, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands. r.j.deboer@bio.uu.nl
authors.forename: Rob J
authors.initials: RJ
authors.lastname: De Boer
authors.forename: Vitaly V
authors.initials: VV
authors.lastname: Ganusov
authors.forename: Dejan
authors.initials: D
authors.lastname: Milutinović
authors.forename: Philip D
authors.initials: PD
authors.lastname: Hodgkin
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005452:Fluoresceins; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008433:Mathematics; D008954:Models, Biological; D013388:Succinimides; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007376:Interleukin-2; D013388:Succinimides