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. 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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
Immunity & ageing - 19(2022), 1 vom: 23. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Matthe, Diana M. [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
Aging |
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| Anmerkungen: |
© The Author(s) 2022 |
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| doi: |
10.1186/s12979-022-00273-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
OLC2129895875 |
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| 520 | |a 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. | ||
| 650 | 4 | |a Telomere shortening | |
| 650 | 4 | |a Telomerase | |
| 650 | 4 | |a CD4-positive T-lymphocytes | |
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| 650 | 4 | |a Aging | |
| 700 | 1 | |a Thoma, Oana-Maria |4 aut | |
| 700 | 1 | |a Sperka, Tobias |4 aut | |
| 700 | 1 | |a Neurath, Markus F. |4 aut | |
| 700 | 1 | |a Waldner, Maximilian J. |4 aut | |
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