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How Naive T-Cell Clone Counts Are Shaped By Heterogeneous Thymic Output and Homeostatic Proliferation

The specificity of T cells is that each T cell has only one T cell receptor (TCR). A T cell clone represents a collection of T cells with the same TCR sequence. Thus, the number of different T cell clones in an organism reflects the number of different T cell receptors (TCRs) that arise from recombi...

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Autores principales: Dessalles, Renaud, Pan, Yunbei, Xia, Mingtao, Maestrini, Davide, D’Orsogna, Maria R., Chou, Tom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891377/
https://www.ncbi.nlm.nih.gov/pubmed/35250963
http://dx.doi.org/10.3389/fimmu.2021.735135
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author Dessalles, Renaud
Pan, Yunbei
Xia, Mingtao
Maestrini, Davide
D’Orsogna, Maria R.
Chou, Tom
author_facet Dessalles, Renaud
Pan, Yunbei
Xia, Mingtao
Maestrini, Davide
D’Orsogna, Maria R.
Chou, Tom
author_sort Dessalles, Renaud
collection PubMed
description The specificity of T cells is that each T cell has only one T cell receptor (TCR). A T cell clone represents a collection of T cells with the same TCR sequence. Thus, the number of different T cell clones in an organism reflects the number of different T cell receptors (TCRs) that arise from recombination of the V(D)J gene segments during T cell development in the thymus. TCR diversity and more specifically, the clone abundance distribution, are important factors in immune functions. Specific recombination patterns occur more frequently than others while subsequent interactions between TCRs and self-antigens are known to trigger proliferation and sustain naive T cell survival. These processes are TCR-dependent, leading to clone-dependent thymic export and naive T cell proliferation rates. We describe the heterogeneous steady-state population of naive T cells (those that have not yet been antigenically triggered) by using a mean-field model of a regulated birth-death-immigration process. After accounting for random sampling, we investigate how TCR-dependent heterogeneities in immigration and proliferation rates affect the shape of clone abundance distributions (the number of different clones that are represented by a specific number of cells, or “clone counts”). By using reasonable physiological parameter values and fitting predicted clone counts to experimentally sampled clone abundances, we show that realistic levels of heterogeneity in immigration rates cause very little change to predicted clone-counts, but that modest heterogeneity in proliferation rates can generate the observed clone abundances. Our analysis provides constraints among physiological parameters that are necessary to yield predictions that qualitatively match the data. Assumptions of the model and potentially other important mechanistic factors are discussed.
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spelling pubmed-88913772022-03-04 How Naive T-Cell Clone Counts Are Shaped By Heterogeneous Thymic Output and Homeostatic Proliferation Dessalles, Renaud Pan, Yunbei Xia, Mingtao Maestrini, Davide D’Orsogna, Maria R. Chou, Tom Front Immunol Immunology The specificity of T cells is that each T cell has only one T cell receptor (TCR). A T cell clone represents a collection of T cells with the same TCR sequence. Thus, the number of different T cell clones in an organism reflects the number of different T cell receptors (TCRs) that arise from recombination of the V(D)J gene segments during T cell development in the thymus. TCR diversity and more specifically, the clone abundance distribution, are important factors in immune functions. Specific recombination patterns occur more frequently than others while subsequent interactions between TCRs and self-antigens are known to trigger proliferation and sustain naive T cell survival. These processes are TCR-dependent, leading to clone-dependent thymic export and naive T cell proliferation rates. We describe the heterogeneous steady-state population of naive T cells (those that have not yet been antigenically triggered) by using a mean-field model of a regulated birth-death-immigration process. After accounting for random sampling, we investigate how TCR-dependent heterogeneities in immigration and proliferation rates affect the shape of clone abundance distributions (the number of different clones that are represented by a specific number of cells, or “clone counts”). By using reasonable physiological parameter values and fitting predicted clone counts to experimentally sampled clone abundances, we show that realistic levels of heterogeneity in immigration rates cause very little change to predicted clone-counts, but that modest heterogeneity in proliferation rates can generate the observed clone abundances. Our analysis provides constraints among physiological parameters that are necessary to yield predictions that qualitatively match the data. Assumptions of the model and potentially other important mechanistic factors are discussed. Frontiers Media S.A. 2022-02-17 /pmc/articles/PMC8891377/ /pubmed/35250963 http://dx.doi.org/10.3389/fimmu.2021.735135 Text en Copyright © 2022 Dessalles, Pan, Xia, Maestrini, D’Orsogna and Chou https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Dessalles, Renaud
Pan, Yunbei
Xia, Mingtao
Maestrini, Davide
D’Orsogna, Maria R.
Chou, Tom
How Naive T-Cell Clone Counts Are Shaped By Heterogeneous Thymic Output and Homeostatic Proliferation
title How Naive T-Cell Clone Counts Are Shaped By Heterogeneous Thymic Output and Homeostatic Proliferation
title_full How Naive T-Cell Clone Counts Are Shaped By Heterogeneous Thymic Output and Homeostatic Proliferation
title_fullStr How Naive T-Cell Clone Counts Are Shaped By Heterogeneous Thymic Output and Homeostatic Proliferation
title_full_unstemmed How Naive T-Cell Clone Counts Are Shaped By Heterogeneous Thymic Output and Homeostatic Proliferation
title_short How Naive T-Cell Clone Counts Are Shaped By Heterogeneous Thymic Output and Homeostatic Proliferation
title_sort how naive t-cell clone counts are shaped by heterogeneous thymic output and homeostatic proliferation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891377/
https://www.ncbi.nlm.nih.gov/pubmed/35250963
http://dx.doi.org/10.3389/fimmu.2021.735135
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