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Multiscale physiologically-based model of age-dependent CD4+ T-lymphocyte homeostasis.

Victoria Kulesh1,2,3, Kirill Peskov1,2,4, Gabriel Helmlinger5

  • 1Research Center of Model-Informed Drug Development, Sechenov First Moscow State Medical University, Moscow, Russia.

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|February 20, 2026
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Summary

A new model describes CD4+ T-lymphocyte homeostasis across lifespan, revealing age-related changes in cell dynamics and thymic output are key to immune health. This tool aids in predicting T-cell responses to interventions.

Keywords:
CD4+ T-lymphocytesage-dependent homeostasisagingmechanistic modelingthymectomythymus involution

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Area of Science:

  • Immunology
  • Systems Biology
  • Computational Biology

Background:

  • CD4+ T-lymphocyte homeostasis is crucial for immune function throughout human life.
  • Understanding age-related changes in T-cell dynamics is essential for immune health.
  • Existing models may not fully capture the complexity of T-cell lifespan dynamics.

Purpose of the Study:

  • To develop a mechanistic, physiologically-based model of CD4+ T-lymphocyte homeostasis.
  • To incorporate age-dependent factors, cell maturation, differentiation, and migration.
  • To analyze the impact of aging on distinct CD4+ T-cell subpopulations.

Main Methods:

  • Integrated quantitative data on CD4+ T-cell concentrations and kinetic parameters.
  • Developed a system of ordinary differential equations for thymocyte and CD4+ T-cell subpopulations.
  • Modeled five physiological compartments and tested age-related empirical functions.

Main Results:

  • Identified age-related shifts in cell proliferation, differentiation, survival, and migration as key determinants.
  • Reduced thymic output significantly impacts CD4+ T-cell homeostasis.
  • Model simulations showed compensatory mechanisms are insufficient after thymectomy.

Conclusions:

  • The developed model provides a robust, multiscale quantitative framework for T-cell dynamics.
  • It aids in predicting CD4+ T-cell behavior under various physiological conditions.
  • The model can assess the impact of interventions on immune homeostasis.