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Telomerase deficiency reflects age-associated changes in CD4+ T cells

BACKGROUND: Amongst other systemic changes, aging leads to an immune dysfunction. On the molecular level, a hallmark of aging is telomere shortening. The functional relevance of telomerase, an enzyme capable of elongating telomeres in T cells upon antigen stimulation, is not fully understood. Studyi...

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Autores principales: Matthe, Diana M., Thoma, Oana-Maria, Sperka, Tobias, Neurath, Markus F., Waldner, Maximilian J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941756/
https://www.ncbi.nlm.nih.gov/pubmed/35321714
http://dx.doi.org/10.1186/s12979-022-00273-0
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author Matthe, Diana M.
Thoma, Oana-Maria
Sperka, Tobias
Neurath, Markus F.
Waldner, Maximilian J.
author_facet Matthe, Diana M.
Thoma, Oana-Maria
Sperka, Tobias
Neurath, Markus F.
Waldner, Maximilian J.
author_sort Matthe, Diana M.
collection PubMed
description BACKGROUND: Amongst other systemic changes, aging leads to an immune dysfunction. On the molecular level, a hallmark of aging is telomere shortening. The functional relevance of telomerase, an enzyme capable of elongating telomeres in T cells upon antigen stimulation, is not fully understood. Studying the impact of telomere shortening on CD4+ T cells and especially Th1 effector function can provide a better understanding on immune dysfunctions in elderly. RESULTS: We investigated T cell numbers and differentiation in telomerase-deficient (mTerc−/−) mice under steady-state conditions and the functional role of telomerase in CD4+ T cells using in vitro stimulation and Th1 polarization protocols by comparing T cells from mTerc−/− and control mice. We report reduced relative CD4+ T cell numbers in blood and secondary lymphoid organs and a relative decline in the naïve T cell population in thymus, blood and spleen of mTerc−/− mice compared to control mice. Importantly, after in vitro polarization, mTerc−/− G3 CD4+ T cells showed higher numbers of IFNγ-producing cells and reduced expression of CD28. Notably, telomerase-deficient T cells were more susceptible to inhibition of Th1 polarization by IL-6 in vitro. These results demonstrate that telomerase deficiency recapitulates several changes of CD4+ T cells seen in aged humans regarding the naïve T cell population, expression of CD28 and cytokine production. CONCLUSION: Our data suggest that telomere shortening could play a key role in the aging of T cell immunity, with clinical implications for immune diseases and tumor development and that mTerc−/− mice are a suitable model to study aging-related defects of adaptive immunity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-022-00273-0.
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spelling pubmed-89417562022-03-24 Telomerase deficiency reflects age-associated changes in CD4+ T cells Matthe, Diana M. Thoma, Oana-Maria Sperka, Tobias Neurath, Markus F. Waldner, Maximilian J. Immun Ageing Research BACKGROUND: Amongst other systemic changes, aging leads to an immune dysfunction. On the molecular level, a hallmark of aging is telomere shortening. The functional relevance of telomerase, an enzyme capable of elongating telomeres in T cells upon antigen stimulation, is not fully understood. Studying the impact of telomere shortening on CD4+ T cells and especially Th1 effector function can provide a better understanding on immune dysfunctions in elderly. RESULTS: We investigated T cell numbers and differentiation in telomerase-deficient (mTerc−/−) mice under steady-state conditions and the functional role of telomerase in CD4+ T cells using in vitro stimulation and Th1 polarization protocols by comparing T cells from mTerc−/− and control mice. We report reduced relative CD4+ T cell numbers in blood and secondary lymphoid organs and a relative decline in the naïve T cell population in thymus, blood and spleen of mTerc−/− mice compared to control mice. Importantly, after in vitro polarization, mTerc−/− G3 CD4+ T cells showed higher numbers of IFNγ-producing cells and reduced expression of CD28. Notably, telomerase-deficient T cells were more susceptible to inhibition of Th1 polarization by IL-6 in vitro. These results demonstrate that telomerase deficiency recapitulates several changes of CD4+ T cells seen in aged humans regarding the naïve T cell population, expression of CD28 and cytokine production. CONCLUSION: Our data suggest that telomere shortening could play a key role in the aging of T cell immunity, with clinical implications for immune diseases and tumor development and that mTerc−/− mice are a suitable model to study aging-related defects of adaptive immunity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-022-00273-0. BioMed Central 2022-03-23 /pmc/articles/PMC8941756/ /pubmed/35321714 http://dx.doi.org/10.1186/s12979-022-00273-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Matthe, Diana M.
Thoma, Oana-Maria
Sperka, Tobias
Neurath, Markus F.
Waldner, Maximilian J.
Telomerase deficiency reflects age-associated changes in CD4+ T cells
title Telomerase deficiency reflects age-associated changes in CD4+ T cells
title_full Telomerase deficiency reflects age-associated changes in CD4+ T cells
title_fullStr Telomerase deficiency reflects age-associated changes in CD4+ T cells
title_full_unstemmed Telomerase deficiency reflects age-associated changes in CD4+ T cells
title_short Telomerase deficiency reflects age-associated changes in CD4+ T cells
title_sort telomerase deficiency reflects age-associated changes in cd4+ t cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941756/
https://www.ncbi.nlm.nih.gov/pubmed/35321714
http://dx.doi.org/10.1186/s12979-022-00273-0
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