TY  - JOUR
A1  - Robert, Philippe A.
A1  - Kunze-Schumacher, Heike
A1  - Greiff, Victor
A1  - Krueger, Andreas
T1  - Modeling the dynamics of T-cell development in the thymus
T2  - Entropy
N2  - 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.
KW  - thymic selection
KW  - T-cell development
KW  - T-cell receptor (TCR)
KW  - mathematical modeling
KW  - multi-scale models
KW  - complex systems
KW  - ordinary differential equations (ODE)
KW  - agent-based models
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/61122
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-611226
SN  - 1099-4300
N1  - 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).
VL  - 23
IS  - 4, art. 437
SP  - 1
EP  - 36
PB  - MDPI
CY  - Basel
ER  -