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

Matthe D, Thoma OM, Sperka T, Neurath M, Waldner M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 19

Journal Issue: 1

DOI: 10.1186/s12979-022-00273-0

Abstract

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.

Authors with CRIS profile

Involved external institutions

Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut (FLI) Germany (DE)

How to cite

APA:

Matthe, D., Thoma, O.-M., Sperka, T., Neurath, M., & Waldner, M. (2022). Telomerase deficiency reflects age-associated changes in CD4+T cells. Immunity & Ageing, 19(1). https://dx.doi.org/10.1186/s12979-022-00273-0

MLA:

Matthe, Diana, et al. "Telomerase deficiency reflects age-associated changes in CD4+T cells." Immunity & Ageing 19.1 (2022).

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