T lymphocyte senescence is attenuated in Parkinson's disease

J Neuroinflammation. 2021 Oct 13;18(1):228. doi: 10.1186/s12974-021-02287-9.

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.

Keywords: Ageing markers; Immunosenescence; Parkinson’s disease; T lymphocytes.

MeSH terms

  • Aged
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Cellular Senescence / physiology*
  • Female
  • Flow Cytometry / methods
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / pathology
  • Male
  • Middle Aged
  • Parkinson Disease / immunology
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology