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Systems Immunology for Modeling T cell Dynamics

Abstract : The integration of the immune system, as a complex ecosystem that organizes through dynamic multi-level processes with cell proliferation, diversity and clonal selection of lymphocytes, in various tissues and through time, requires systems immunology. Cell proliferation, is the common characteristic of all biological systems, but the quantification, modeling and control remains a challenge. The goal is to model the dynamics heterogeneity of T cell populations that continuously differentiate and turnover in lymphoid tissues. How lymphocytes modify their behavior in response to aging and perturbations of the organism, but also according to genetic origins, is a key to understand physiology and pathologies. This requires specific experimental methods and modelling. We designed mice models, associated to multi-level and multi-parameter approaches. The analysis of phenome, cell cycle, and repertome, with single-cell multi-parameter flow cytometry analysis, allows to quantify cell proliferation by crossing various approaches: (i) using lymphocyte sensitivity to depletion of dividing cell, and their recovery post-depletion, (ii) in vivo staining of cells through pulse/chase of DNA analog, to quantify their progression across the cell cycle phases. Population model and discrete multi-agent system were developed, using visual modeling language, with transition diagrams. Fitting on experimental data allowed to infer parameters values and validate the models. Modeling allows to reconstruct the T cell dynamics from the thymus to the migration in spleen, through cell transitions and interactions, with estimation of cell proliferation, differentiation and selection rates. Age of organism is a parameter that influences the behavior and reconstitution capacities of the immune system. Homeostatic regulations occur in young mice, post a transient depletion of dividing cells, and after an immune response. By contrast, in old mice the lymphocyte reconstitution and the repertoire diversity are perturbed, with emergence of polyclonal expansions. Then, immunosuppression accelerates biological aging, by reduction of lymphocyte repertoire diversity. Systems immunology allows to reveal that T cell heterogeneity dynamics, in various tissues, is not only driven by the age of the organism, but also by the genetic origins, that influence the lymphocyte proliferation capacities and thus sensitivity to treatments.
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Contributor : Véronique Thomas-Vaslin Connect in order to contact the contributor
Submitted on : Thursday, January 28, 2021 - 6:22:55 PM
Last modification on : Tuesday, February 2, 2021 - 3:29:49 AM


  • HAL Id : hal-02409330, version 1


Véronique Thomas-Vaslin. Systems Immunology for Modeling T cell Dynamics. 52nd Annual Meeting of the French Society for Immunology, Nov 2019, Nantes, France. ⟨hal-02409330⟩



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