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T lymphocyte senescence is attenuated in Parkinson's disease.

Accepted version
Peer-reviewed

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Article

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Authors

Jensen, Melanie 
Papastavrou, Vanesa 
Scott, Kirsten M 
Kolenda, Claire 

Abstract

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.

Description

Keywords

Ageing markers, Immunosenescence, Parkinson’s disease, T lymphocytes, Aged, CD8-Positive T-Lymphocytes, Cellular Senescence, Female, Flow Cytometry, Humans, Leukocytes, Mononuclear, Male, Middle Aged, Parkinson Disease, T-Lymphocytes

Journal Title

J Neuroinflammation

Conference Name

Journal ISSN

1742-2094
1742-2094

Volume Title

18

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Michael J. Fox Foundation (MJFF) (14912)
Wellcome Trust (106565/Z/14/Z)
Medical Research Council (MR/R007446/1)