Lifelong dynamics of human CD4+CD25+ regulatory T cells: insights from in vivo data and mathematical modeling.

Détails

ID Serval
serval:BIB_440F62F1B598
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Lifelong dynamics of human CD4+CD25+ regulatory T cells: insights from in vivo data and mathematical modeling.
Périodique
Journal of Theoretical Biology
Auteur⸱e⸱s
Baltcheva I., Codarri L., Pantaleo G., Le Boudec J.Y.
ISSN
1095-8541[electronic], 0022-5193[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
266
Numéro
2
Pages
307-322
Langue
anglais
Résumé
Despite their limited proliferation capacity, regulatory T cells (T(regs)) constitute a population maintained over the entire lifetime of a human organism. The means by which T(regs) sustain a stable pool in vivo are controversial. Using a mathematical model, we address this issue by evaluating several biological scenarios of the origins and the proliferation capacity of two subsets of T(regs): precursor CD4(+)CD25(+)CD45RO(-) and mature CD4(+)CD25(+)CD45RO(+) cells. The lifelong dynamics of T(regs) are described by a set of ordinary differential equations, driven by a stochastic process representing the major immune reactions involving these cells. The model dynamics are validated using data from human donors of different ages. Analysis of the data led to the identification of two properties of the dynamics: (1) the equilibrium in the CD4(+)CD25(+)FoxP3(+)T(regs) population is maintained over both precursor and mature T(regs) pools together, and (2) the ratio between precursor and mature T(regs) is inverted in the early years of adulthood. Then, using the model, we identified three biologically relevant scenarios that have the above properties: (1) the unique source of mature T(regs) is the antigen-driven differentiation of precursors that acquire the mature profile in the periphery and the proliferation of T(regs) is essential for the development and the maintenance of the pool; there exist other sources of mature T(regs), such as (2) a homeostatic density-dependent regulation or (3) thymus- or effector-derived T(regs), and in both cases, antigen-induced proliferation is not necessary for the development of a stable pool of T(regs). This is the first time that a mathematical model built to describe the in vivo dynamics of regulatory T cells is validated using human data. The application of this model provides an invaluable tool in estimating the amount of regulatory T cells as a function of time in the blood of patients that received a solid organ transplant or are suffering from an autoimmune disease.
Mots-clé
lymphocytic choriomeningitis virus, peripheral-blood, immune-responses, cord blood, cd4(+), antigen, foxp3, thymus, proliferation, population, Mathematical model, Regulatory T cells, Lifelong in vivo dynamics, Maximum likelihood estimation
Pubmed
Web of science
Création de la notice
08/09/2010 15:15
Dernière modification de la notice
20/08/2019 13:48
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