Modeling the dynamics of T-cell development in the thymus

  • The thymus hosts the development of a specific type of adaptive immune cells called T cells. T cells orchestrate the adaptive immune response through recognition of antigen by the highly variable T-cell receptor (TCR). T-cell development is a tightly coordinated process comprising lineage commitment, somatic recombination of Tcr gene loci and selection for functional, but non-self-reactive TCRs, all interspersed with massive proliferation and cell death. Thus, the thymus produces a pool of T cells throughout life capable of responding to virtually any exogenous attack while preserving the body through self-tolerance. The thymus has been of considerable interest to both immunologists and theoretical biologists due to its multi-scale quantitative properties, bridging molecular binding, population dynamics and polyclonal repertoire specificity. Here, we review experimental strategies aimed at revealing quantitative and dynamic properties of T-cell development and how they have been implemented in mathematical modeling strategies that were reported to help understand the flexible dynamics of the highly dividing and dying thymic cell populations. Furthermore, we summarize the current challenges to estimating in vivo cellular dynamics and to reaching a next- generation multi-scale picture of T-cell development.
Author:Philippe A. RobertORCiD, Heike Kunze-SchumacherORCiDGND, Victor GreiffORCiDGND, Andreas KruegerORCiDGND
Parent Title (English):Entropy
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/04/08
Date of first Publication:2021/04/08
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2021/06/09
Tag:T-cell development; T-cell receptor (TCR); agent-based models; complex systems; mathematical modeling; multi-scale models; ordinary differential equations (ODE); thymic selection
Issue:4, art. 437
Page Number:36
First Page:1
Last Page:36
Support was provided by The Helmsley Charitable Trust (#2019PG-T1D011, to V.G.), UiO World-Leading Research Community (to V.G.), UiO:LifeSciences Convergence Environment Immunolingo (to V.G.), EU Horizon 2020 iReceptorplus (#825821) (to V.G.), a Research Council of Norway FRIPRO project (#300740, to V.G.). Work on quantitative biology of T-cell development in the laboratory of A.K. is funded by the German Research Foundation (DFG, grant KR2320/6-1).
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0