Telomere Erosion in Memory T Cells Induced by Telomerase Inhibition at the Site of Antigenic Challenge In Vivo
Open accessAbstract
The extent of human memory T cell proliferation, differentiation, and telomere erosion that occurs after a single episode of immune challenge in vivo is unclear. To investigate this, we injected tuberculin purified protein derivative (PPD) into the skin of immune individuals and isolated responsive T cells from the site of antigenic challenge at different times. PPD-specific CD4+ T cells proliferated and differentiated extensively in the skin during this secondary response. Furthermore, significant telomere erosion occurred in specific T cells that respond in the skin, but not in those that are found in the blood from the same individuals. Tissue fluid obtained from the site of PPD challenge in the skin inhibited the induction of the enzyme telomerase in T cells in vitro. Antibody inhibition studies indicated that type I interferon (IFN), which was identified at high levels in the tissue fluid and by immunohistology, was responsible in part for the telomerase inhibition. Furthermore, the addition of IFN-α to PPD-stimulated CD4+ T cells directly inhibited telomerase activity in vitro. Therefore, these results suggest that the rate of telomere erosion in proliferating, antigen-specific CD4+ T cells may be accelerated by type I IFN during a secondary response in vivo.
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Inflammatory cytokines such as IFN-alpha can activate p38 in non-senescent T cells and inhibit proliferation and telomerase activity.
“In this context, inflammatory cytokines such as IFN- , can activate p38 in non-senescent T cells and this can inhibit proliferation and telomerase activity [29, 34, 61].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [61]
Inflammatory cytokines such as IFN-alpha can inhibit telomerase in T cells and induce telomere erosion, which lends support to the possibility that short telomeres are a secondary consequence of chronic systemic inflammation.
“The fact that inflammatory cytokines such as IFN can inhibit telomerase in T cells and induce telomere erosion in these cells [29, 34, 61] lends support to the latter possibility.”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [61]
There is an interrelationship between senescence, nutrition and inflammation in regulating T cell function.
“the new awareness of the interrelationship between senescence, nutrition and inflammation in regulating T cell function [25, 29, 61].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [61]
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References 43 · Cited by 111
- Authors
- Reed, J. R., Vukmanovic-Stejic, M., Fletcher, J. M., Soares, M. V. D., Cook, J. E., Orteu, C. H., Jackson, S. E., Birch, K. E., Foster, G. R., Salmon, M., Beverley, P. C. L., Rustin, M. H. A., & Akbar, A. N.
- Affiliations
- The Royal Free Hospital (GB)
- 1Department of Immunology and Molecular Pathology, Division of Infection and Immunity, University College London, London, W1T 4JF, England, UK
- University College London (GB)
- Jenner Institute (GB)
- Queen Mary University of London (GB)
- University of Birmingham (GB)
- ORCID
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2004-05-17
- Volume
- 199
- Issue
- 10
- Pages
- 1433-1443
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2211820
- OpenAlex
- W2141824651
- Cited by
- 111
- References
- 43
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 2 · 2018: 8 · 2017: 4 · 2016: 3 · 2015: 2 · 2014: 7 · 2013: 7 · 2012: 8
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
- Funders
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- telomere shortening, memory T cells, telomerase inhibition, type I interferon, interferon-alpha, CD4+ T cells, purified protein derivative, secondary immune response, T cell proliferation, T cell differentiation, interstitial fluid
- MeSH terms
- BCG Vaccine, Cells, Cultured, Enzyme Inhibitors, Humans, Immunologic Memory, Lymphocyte Activation, T-Lymphocytes, CD4-Positive T-Lymphocytes, Telomere, In Situ Hybridization, Fluorescence, Telomerase
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