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T lymphocyte senescence is attenuated in Parkinson’s disease

Lookup NU author(s): Claire Kolenda, Dr Craig Parker, Dr Carmen Martin-RuizORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2021, The Author(s).Background: Immune involvement is well-described in Parkinson’s disease (PD), including an adaptive T lymphocyte response. Given the increasing prevalence of Parkinson’s disease in older age, age-related dysregulation of T lymphocytes may be relevant in this disorder, and we have previously observed changes in age-associated CD8+ T cell subsets in mid-stage PD. This study aimed to further characterise T cell immunosenescence in newly diagnosed PD patients, including shifts in CD4+ and CD8+ subpopulations, and changes in markers of cellular ageing in CD8+ T lymphocytes. Methods: Peripheral blood mononuclear cells were extracted from the blood of 61 newly diagnosed PD patients and 63 age- and sex-matched controls. Flow cytometric analysis was used for immunophenotyping of CD8+ and CD4+ lymphocyte subsets, and analysis of recent thymic emigrant cells. Telomere length within CD8+ T lymphocytes was assessed, as well as the expression of the telomerase reverse transcriptase enzyme (hTERT), and the cell-ageing markers p16INK4a and p21CIP1/Waf1. Results: The number of CD8+ TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16INK4a in CD8+ lymphocytes was also lower in patients versus controls. Chronic latent CMV infection was associated with increased senescent CD8+ lymphocytes in healthy controls, but this shift was less apparent in PD patients. Conclusions: Taken together, our data demonstrate a reduction in CD8+ T cell replicative senescence which is present at the earliest stages of Parkinson’s disease.


Publication metadata

Author(s): Kouli A, Jensen M, Papastavrou V, Scott KM, Kolenda C, Parker C, Solim IH, Camacho M, Martin-Ruiz C, Williams-Gray CH

Publication type: Article

Publication status: Published

Journal: Journal of Neuroinflammation

Year: 2021

Volume: 18

Issue: 1

Online publication date: 13/10/2021

Acceptance date: 01/10/2021

Date deposited: 22/07/2022

ISSN (electronic): 1742-2094

Publisher: BioMed Central Ltd

URL: https://doi.org/10.1186/s12974-021-02287-9

DOI: 10.1186/s12974-021-02287-9


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Funding

Funder referenceFunder name
14912
106565/Z/14/Z
BRC-1215-20014
Cambridge Centre for Parkinson-Plus
MR/R007446/1
Onassis Foundation
Wolfson College, Cambridge

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