Abstract
BackgroundA wealth of evidence implicates both central and peripheral immune changes as contributing to the pathogenesis of Parkinson’s disease (PD). It is critical to better understand this aspect of PD given that it is a tractable target for disease-modifying therapy. Age-related changes are known to occur in the immune system (immunosenescence) and might be of particular relevance in PD given that its prevalence rises with increasing age. We therefore sought to investigate this with respect to T cell replicative senescence, a key immune component of human ageing.MethodsPeripheral blood mononuclear cells were extracted from blood samples from 41 patients with mild PD (Hoehn and Yahr stages 1–2, mean (SD) disease duration 4.3 (1.2) years) and 41 age- and gender-matched controls. Immunophenotyping was performed with flow cytometry using markers of T lymphocyte activation and senescence (CD3, CD4, CD8, HLA-DR, CD38, CD28, CCR7, CD45RA, CD57, CD31). Cytomegalovirus (CMV) serology was measured given its proposed relevance in driving T cell senescence.ResultsMarkers of replicative senescence in the CD8+ population were strikingly reduced in PD cases versus controls (reduced CD57 expression (p = 0.005), reduced percentage of ‘late differentiated’ CD57loCD28hi cells (p = 0.007) and ‘TEMRA’ cells (p = 0.042)), whilst expression of activation markers (CD28) was increased (p = 0.005). This was not driven by differences in CMV seropositivity. No significant changes were observed in the CD4 population.ConclusionsThis study demonstrates for the first time that the peripheral immune profile in PD is distinctly atypical for an older population, with a lack of the CD8+ T cell replicative senescence which characterises normal ageing. This suggests that ‘abnormal’ immune ageing may contribute to the development of PD, and markers of T cell senescence warrant further investigation as potential biomarkers in this condition.
Highlights
A wealth of evidence implicates both central and peripheral immune changes as contributing to the pathogenesis of Parkinson’s disease (PD)
This study demonstrates for the first time that the peripheral immune profile in PD is distinctly atypical for a more elderly population, with a lack of the CD8+ T cell replicative senescence which characterises normal ageing
Other authors have reported phenotypic alterations in the T lymphocyte population in PD, these alterations have mainly been restricted to CD4+ cell subsets with conflicting findings [9, 32, 33] and we found no changes in the CD4+ T cell pool in this study
Summary
A wealth of evidence implicates both central and peripheral immune changes as contributing to the pathogenesis of Parkinson’s disease (PD). Age-related changes are known to occur in the immune system (immunosenescence) and might be of particular relevance in PD given that its prevalence rises with increasing age. Progression of CD8 T cells to a senescent state is characterised by the loss of surface expression of the co-stimulatory molecule CD28 and expression of CD57 [17, 20]. In vivo, both TEMRA and CD28loCD57hi CD8+ cells are increased in frequency in patients with chronic infections, e.g. HIV, as well as in older age [21,22,23]. Loss of thymic T cell production can be measured in the CD4 pool as a loss of CD4+ recent thymic emigrants (RTEs), CD4+ naïve cells that co-express CD31 [19]
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