13/02/2026
This article presents a physiologically-based model of age-dependent CD4+ T-lymphocyte homeostasis across the human lifespan, capturing maturation, differentiation, and migration across five physiological compartments (thymus, blood, lymphoid tissue, gastrointestinal tract, and lungs).
The model consists of a system of ODEs describing four thymocyte and six CD4+ T-lymphocyte subpopulations and integrates published quantitative blood and tissue data on cell concentrations with experimental kinetic estimates. Age-dependent immune homeostasis is represented through explicit thymic involution and age-related changes in kinetic parameters, while regulatory mechanisms that compensate for reduced thymic output are also incorporated.
The framework identifies key drivers of CD4+ T-cell homeostasis under physiological conditions and perturbations and represents a quantitative tool predict CD4+ T-cell dynamics and assess the impact of physiological changes or therapeutic interventions.
