Dynamics of T cell receptor distributions following acute thymic atrophy and resumption

DOI10.3934/MBE.2020002zbMATH Open1470.92058arXiv1905.12179OpenAlexW2976994347WikidataQ91298237 ScholiaQ91298237MaRDI QIDQ2045649FDOQ2045649

Authors: Stephanie Lewkiewicz, Tom Chou, Yao-Li Chuang 

Publication date: 13 August 2021

Published in: Mathematical Biosciences and Engineering (Search for Journal in Brave)

Abstract: Naive human T cells are produced in the thymus, which atrophies abruptly and severely in response to physical or psychological stress. To understand how an instance of stress affects the size and "diversity" of the peripheral naive T cell pool, we derive a mean-field autonomous ODE model of T cell replenishment that allows us to track the clone abundance distribution (the mean number of different TCRs each represented by a specific number of cells). We identify equilibrium solutions that arise at different rates of T cell production, and derive analytic approximations to the dominant eigenvalues and eigenvectors of the problem linearized about these equilibria. From the forms of the eigenvalues and eigenvectors, we estimate rates at which counts of clones of different sizes converge to and depart from equilibrium values--that is, how the number of clones of different sizes "adjust" to the changing rate of T cell production. Under most physiologically realistic realizations of our model, the dominant eigenvalue (representing the slowest dynamics of the clone abundance distribution) scales as a power law in the thymic output for low output levels, but saturates at higher T cell production rates. Our analysis provides a framework for quantitatively understanding how the clone abundance distributions evolve under small changes in the overall T cell production rate by the thymus.

Full work available at URL: https://arxiv.org/abs/1905.12179

Recommendations

• Dynamics of T cell activation threshold tuning
• Thymic selection of T cells as diffusion with intermittent traps
• The effects of affinity mediated clonal expansion of premigrant thymocytes on the periphery T-cell repertoire
• An improved model of T cell development in the thymus and its stability analysis
• Stability of a diverse immunological memory is determined by T cell population dynamics
• Germinal center dynamics during acute and chronic infection
• T cell development in the thymus: from periodic seeding to constant output
• Explaining high alloreactivity as a quantitative consequence of affinity-driven thymocyte selection
• A phenomenological approach to the dynamics of activation and clonal expansion of \(T\) cells

zbMATH Keywords

clone abundance distributionnaive T cell diversitythymic output

Mathematics Subject Classification ID

Physiology (general) (92C30)

Cites Work

• Quantifying T lymphocyte turnover
• Immigration-induced phase transition in a regulated multispecies birth-death process
• How many TCR clonotypes does a body maintain?
• A mathematical model of the effects of aging on naive T cell populations and diversity

Cited In (3)

• Insights into the mechanisms of thymus involution and regeneration by modeling the glucocorticoid-induced perturbation of thymocyte populations dynamics
• How many TCR clonotypes does a body maintain?
• Decline in excision circles requires homeostatic renewal or homeostatic death of naive T cells

This page was built for publication: Dynamics of T cell receptor distributions following acute thymic atrophy and resumption

Report a bug (only for logged in users!)Click here to report a bug for this page (MaRDI item Q2045649)