T lymphocyte senescence is attenuated in Parkinson’s disease
Antonina Kouli, Melanie P. Jensen, Vanesa Papastavrou, Kirsten M. Scott, Claire Kolenda, Craig Parker, Imtiaz H. Solim, Marta Camacho, Carmen Martín-Ruiz, Caroline H. Williams‐Gray
Abstract
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 p16 INK4a and p21 CIP1/Waf1 . Results The number of CD8 + TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16 INK4a 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.