T lymphocyte senescence is attenuated in Parkinson\u2019s disease

Antonina Kouli,Caroline H Williams-Gray,Carmen Martin-Ruiz,Vanesa Papastavrou,Craig Parker,Claire Kolenda,Kirsten M Scott,Marta Camacho,Melanie Jensen,Imtiaz H Solim

doi:10.1186/s12974-021-02287-9

Abstract

BackgroundImmune 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.MethodsPeripheral 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.ResultsThe 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.ConclusionsTaken together, our data demonstrate a reduction in CD8+ T cell replicative senescence which is present at the earliest stages of Parkinson’s disease.

Highlights

It is well-recognised that numerous innate and adaptive immune changes occur both in the brain and the periphery in Parkinson’s disease (PD) patients [1], though the precise mechanisms and their role in disease progression are still poorly understood
We found no significant changes in markers of C D4+ replicative senescence in PD versus controls, but this warrants replication given the evidence for altered C D4+ T cell subsets in PD [21, 24,25,26]
We found that leukocyte expression levels of the cellular senescence marker p21 were lower in PD versus controls, whilst lower p16 expression at baseline was associated with faster motor and cognitive progression over 36 months; supporting the hypothesis that immunosenescence is reduced in PD

Summary

Introduction

It is well-recognised that numerous innate and adaptive immune changes occur both in the brain and the periphery in Parkinson’s disease (PD) patients [1], though the precise mechanisms and their role in disease progression are still poorly understood. Age-related immune changes (immunosenescence) may be relevant to diseases like PD for which ageing is a major risk factor. Immunosenescence leads to increased infection susceptibility and reduced effectiveness of vaccines [2]. This is mediated primarily by changes in CD8+ T lymphocytes. 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

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