Journal
IMMUNITY & AGEING
Volume 19, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12979-022-00273-0
Keywords
Telomere shortening; Telomerase; CD4-positive T-lymphocytes; Th1 cells; Aging
Categories
Funding
- Projekt DEAL
- Erlangen Graduate School in Advanced Optical Technologies (SAOT) by the German Research Foundation (DFG)
- German Research Foundation (DFG) within Forschergruppe 2438 (FOR 2438)
- Collaborative Research Center 241 (Transregio 241) Immune-Epithelial Communication in Inflammatory Bowel Diseases
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The research found that in telomerase-deficient mice, there was a reduction in CD4+ T cell numbers and an enhancement in proliferation and Th1 polarization, with increased production of IFN gamma-producing cells and reduced CD28 expression. These results suggest that telomerase deficiency replicates several changes in CD4+ T cells seen in aged humans, highlighting its potential role in T cell immunity aging.
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 naive 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 IFN gamma-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 naive 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.
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