T lymphocyte senescence is attenuated in Parkinson's disease

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.