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T lymphocyte senescence is attenuated in Parkinson's disease.

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dc.contributor.authorKouli, Antonina
dc.contributor.authorJensen, Melanie
dc.contributor.authorPapastavrou, Vanesa
dc.contributor.authorScott, Kirsten M
dc.contributor.authorKolenda, Claire
dc.contributor.authorParker, Craig
dc.contributor.authorSolim, Imtiaz H
dc.contributor.authorCamacho, Marta
dc.contributor.authorMartin-Ruiz, Carmen
dc.contributor.authorWilliams-Gray, Caroline H
dc.contributor.orcidKouli, Antonina [0000-0001-6553-6154]
dc.date.accessioned2021-11-22T14:37:29Z
dc.date.available2021-11-22T14:37:29Z
dc.date.issued2021-10-13
dc.date.updated2021-11-22T14:37:28Z
dc.description.abstract<h4>Background</h4>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<sup>+</sup> 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<sup>+</sup> and CD8<sup>+</sup> subpopulations, and changes in markers of cellular ageing in CD8<sup>+</sup> T lymphocytes.<h4>Methods</h4>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<sup>+</sup> and CD4<sup>+</sup> lymphocyte subsets, and analysis of recent thymic emigrant cells. Telomere length within CD8<sup>+</sup> T lymphocytes was assessed, as well as the expression of the telomerase reverse transcriptase enzyme (hTERT), and the cell-ageing markers p16<sup>INK4a</sup> and p21<sup>CIP1/Waf1</sup>.<h4>Results</h4>The number of CD8<sup>+</sup> TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16<sup>INK4a</sup> in CD8<sup>+</sup> lymphocytes was also lower in patients versus controls. Chronic latent CMV infection was associated with increased senescent CD8<sup>+</sup> lymphocytes in healthy controls, but this shift was less apparent in PD patients.<h4>Conclusions</h4>Taken together, our data demonstrate a reduction in CD8<sup>+</sup> T cell replicative senescence which is present at the earliest stages of Parkinson's disease.
dc.identifier.doi10.17863/CAM.78254
dc.identifier.issn1742-2094
dc.identifier.otherPMC8513368
dc.identifier.other34645462
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330811
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1742-2094
dc.sourcenlmid: 101222974
dc.subjectT lymphocytes
dc.subjectImmunosenescence
dc.subjectParkinson’s Disease
dc.subjectAgeing Markers
dc.titleT lymphocyte senescence is attenuated in Parkinson's disease.
dc.typeArticle
prism.issueIdentifier1
prism.publicationNameJournal of neuroinflammation
prism.volume18
pubs.funder-project-idmedical research council (MR/R007446/1)
pubs.funder-project-idmichael j. fox foundation for parkinson's research (14912)
pubs.funder-project-idMedical Research Council (MR/R007446/1)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1186/s12974-021-02287-9

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