Features of innate and adaptive immunity in patients with Parkinson's disease
Introduction. T cells play a significant role in neuroinflammation in Parkinson's disease (PD). Gamma delta T cells are an underresearched 'minor' subpopulation of T cells. An assessment of the immune system in patients with PD, with a focus on γδТ cells, provides new data on the pathogenesis of neurodegenerative diseases. The aim of the study was to examine the lymphocyte subpopulations, nonclassical γδТ cells, as well as cytokine production in patients with 3 stage PD complicated by motor fluctuations. Materials and methods. We examined 20 patients with 3 stage PD receiving dopaminergic combination therapy (main group) and 20 agematched patients with chronic cerebrovascular disease (comparison group). Considering the suspected role of chronic constipation in maintaining dysbiosis and chronic inflammation in patients with PD, the presence of constipation was an inclusion criterion for this study. The subpopulation profile of the peripheral blood lymphocytes was assessed using flow cytofluorometry, as well as cytokine levels using enzyme linked immunosorbent assay. Results. It was found that the number of mature CD3<sup>+</sup> T cells with αβ or γδ chains as the Tcell receptors (TCR) in the lymphocyte population was significantly lower in patients with PD - median 74% (57.3-83.5)) than in the comparison group (median 80% (73.0-86.0); р = 0.014. There was also a statistically significant reduction in the number of CD3<sup>+</sup>CD56<sup>+</sup> natural killer (NK) T cells in the group of patients with PD vs. the comparison group - 4.7% (1.3-7.7) vs. 7.8% (0.8-24); р = 0.036. At the same time, the number of CD3<sup>-</sup>CD56<sup>+</sup> NK cells was significantly higher in the group of patients with PD (16.4% (9-34)) vs. the comparison group - 8.7% (5-15); р = 0.001. Moreover, the main group had a statistically significantly higher number of activated CD3<sup>-</sup>CD8<sup>+</sup> NK cells - 7% (4.5-13.5) vs. the comparison group - 3.5% (0.86-4.9); р < 0.001. Out of the total number of γδТ cells, the TCRγδ CD4<sup>+</sup>CD8<sup>-</sup> subpopulation was statistically smaller in the group of patients with PD - 13.6% (6.2-27.0) than in the comparison group - 29.8% (4.0-52.1); р = 0.016. The study of cytokine levels in the group of patients with PD showed a significant increase in the induced production of interleukin1β (IL1β), as well as a high (aberrant) spontaneous production of IL10, which was 227.5 pg/ml in patients with PD when the normal range is 0-23 pg/ml. The correlation analysis showed that the TCRγδ CD4<sup>+</sup>CD8<sup>-</sup> subpopulation and cytokines in the group of patients with PD had a statistically significant (p = 0.048) negative correlation with the induced production of IL10 (r = -0.745) and a significant (p = 0.042) positive correlation with the induced production of the proinflammatory cytokine IL1β (r = 0.648). There was a trend towards increased spontaneous production of IL10 (r = -0.602; p = 0.0506) as the level of the TCRγδ CD4<sup>+</sup>CD8<sup>-</sup> T helper cells decreased. Conclusion. Changes were found in the blood of patients with PD, which indicate a chronic inflammatory process: increased number of CD3<sup>-</sup>CD56<sup>+</sup> NK cells, including activated CD3<sup>-</sup>CD8<sup>+</sup> cells, and increased production of proinflammatory cytokine IL1β and antiinflammatory cytokine IL10. A decrease was found in the level of a minor subpopulation of γδT cells, TCRγδ CD4<sup>+</sup>CD8<sup>-</sup>. The correlation found between this subpopulation and the production of proand antiinflammatory cytokines indicates its role in regulation of chronic inflammation in PD.