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Functionality Analysis of Immunoregulatory Cells Stimulated with Dopaminergic Agonists in People Living with Parkinson’s Disease

AY. Regalado-Mustafá, DD. álvarez-Luquín, A. Guevara-Salinas, MA. Bravo-Martinez, EJ. Gallegos-Altamirano, CF. álvarez-Hernández, E. Ichikawa-Escamilla, AM. Peralta-Maza, V. Morales-Ruiz, EE. Sevilla-Reyes, JI. Velasco-Velázquez, JE. Estudillo-Hernández, M. Rodríguez-Violante, LV. Adalid-Peralta (Mexico City, Mexico)

Meeting: 2024 International Congress

Abstract Number: 952

Keywords: Inflammation, Parkinson’s, Pramipexole

Category: Parkinson's Disease: Molecular Mechanisms of Disease

Objective: To evaluate the effect of dopaminergic agonists (DA) on the activation and functionality of regulatory cells in People living with Parkinson’s Disease (PwP).

Background: Neuroinflammation is recognized as a primary mechanism involved in the pathogenesis of Parkinson’s Disease (PD) [1-5]. 

The immune response in PD is characterized by an increase in proinflammatory populations and a decrease in anti-inflammatory populations. A reduction in Treg cells has been observed in untreated PwP, which return to normal levels compared to healthy subjects after one year of treatment with Pramipexole (PPX), along with an increase in the expression of dopaminergic receptors on immune cells [6-14].

Conversely, PwP exhibits a diminished ability of Treg cells to inhibit proliferation. It remains unknown whether the recovery in Treg cell numbers following treatment is accompanied by the restoration of suppressor functionality [15-22].

Method: An observational, cross-sectional, retrospective study was conducted on PwP and controls (Cn) attending a referral center in Mexico between 2021 and 2024.

Venous blood samples were collected, and peripheral blood mononuclear cells (PBMCs) were isolated. PBMCs were labeled with antibodies to identify regulatory and effector T cells, followed by purification using a sorting cytometer. Treg cells were cultured with varying amounts of effector T cells and subsequently analyzed.

Results: 44 participants were included, consisting of 19 Cn and 25 PwP. Among the PwP, 5 had never received treatment (PPX-) and 20 were on pramipexole treatment (PPX+). Sociodemographic variables and scale scores are grouped in Table 1.

The Kruskal-Wallis test revealed significant differences between groups in Percent Inhibition at different effector Treg/T ratios. Post hoc analysis indicated no statistically significant differences between the PPX- and PPX+ groups. The results are detailed in Table 2 and Graph 1.

Conclusion: DA in PwP appears to influence the number of Treg cells positively. However, additional interventions beyond PPX alone may be necessary to fully restore Treg cell functionality. The effects of DA treatment may be insufficient to reverse the proinflammatory effects of the disease, despite their neuroprotective properties. 

It is essential to recruit a larger number of untreated patients to confirm whether differences exist between treated and untreated patients.

Table 1. Sociodemographic, PD-Related Variables.

Table 1. Sociodemographic, PD-Related Variables.

Table 2. Proliferation Inhibition %.

Table 2. Proliferation Inhibition %.

Table 2. Proliferation Inhibition %.

Table 2. Proliferation Inhibition %.

References: 1. Gómez-Chavarín M, Roldan-Roldan G, Morales-Espinosa R, Pérez-Soto G, Torner-Aguilar C. Mecanismos fisiopatológicos involucrados en la enfermedad de Parkinson. Archivos de Neurociencias. 2012;17(1):26–34.
2. Yacoubian TA, Standaert DG. Targets for Neuroprotection in Parkinson’s Disease Talene. Neurodegeneration. 2010;1792(7):676–87.
3. McGeer PL, Itagaki S, Boyes BE, McGeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology. 1988 Aug;38(8):1285–91.
4. Miklossy J, Arai T, Guo JP, Klegeris A, Yu S, McGeer EG, et al. LRRK2 Expression in Normal and Pathologic Human Brain and in Human Cell Lines. Journal of Neuropathology and Experimental Neurology. 2006;65(10):953–63.
5. Nagatsu T, Mogi M, Ichinose H, Togari A. Cytokines in Parkinson’s disease. J Neural Transm Suppl. 2000;(58):143–51.
6. Baba Y, Kuroiwa A, Uitti RJ, Wszolek ZK, Yamada T. Alterations of T-lymphocyte populations in Parkinson disease. Parkinsonism and Related Disorders. 2005;11(8):493–8.
7. Chen Y, Qi B, Xu W, Ma B, Li L, Chen Q, et al. Clinical correlation of peripheral CD4+-cell sub-sets, their imbalance and Parkinson’s disease. Molecular Medicine Reports. 2015;12(4):6105–11.
8. Funk N, Wieghofer P, Grimm S, Schaefer R, Bühring HJ, Gasser T, et al. Characterization of peripheral hematopoietic stem cells and monocytes in Parkinson’s disease. Movement Disorders. 2013;28(3):392–5.
9. Niwa F, Kuriyama N, Nakagawa M, Imanishi J. Effects of peripheral lymphocyte subpopulations and the clinical correlation with Parkinson’s disease. Geriatrics & Gerontology International [Internet]. 2012;12(1):102–7. Available from: http://doi.wiley.com/10.1111/j.1447-0594.2011.00740.x
10. Saunders JAH, Estes KA, Kosloski LM, Allen HE, Dempsey KM, Torres-Russotto DR, et al. CD4+ Regulatory and Effector/Memory T Cell Subsets Profile Motor Dysfunction in Parkinson’s Disease. Journal of Neuroimmune Pharmacology. 2012;7(4):927–38.
11. Rocha NP, Assis F, Scalzo PL, Vieira ÉLM, Barbosa IG, de Souza MS, et al. Reduced Activated T Lymphocytes (CD4+CD25+) and Plasma Levels of Cytokines in Parkinson’s Disease. Molecular Neurobiology. 2018;55(2):1488–97.
12. Ciaramella A, Salani F, Bizzoni F, Pontieri FE, Stefani A, Pierantozzi M, et al. Blood Dendritic Cell Frequency Declines in Idiopathic Parkinson’s Disease and Is Associated with Motor Symptom Severity. PLoS ONE. 2013;8(6).
13. Stevens CH, Rowe D, Morel-Kopp MC, Orr C, Russell T, Ranola M, et al. Reduced T helper and B lymphocytes in Parkinson’s disease. Journal of Neuroimmunology [Internet]. 2012;252(1–2):95–9. Available from: http://dx.doi.org/10.1016/j.jneuroim.2012.07.015
14. Álvarez-Luquín DD, Arce-Sillas A, Leyva-Hernández J, Sevilla-Reyes E, Boll MC, Montes-Moratilla E, et al. Regulatory impairment in untreated Parkinson’s disease is not restricted to Tregs: Other regulatory populations are also involved. Journal of Neuroinflammation. 2019;16(1):1–11.
15. Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3 + regulatory T cells in the human immune system. Nature Reviews Immunology [Internet]. 2010;10(7):490–500. Available from: http://dx.doi.org/10.1038/nri2785
16. Espinosa-Cárdenas R, Arce-Sillas A, Álvarez-Luquin D, Leyva-Hernández J, Montes-Moratilla E, González-Saavedra I, et al. Immunomodulatory effect and clinical outcome in Parkinson’s disease patients on levodopa-pramipexole combo therapy: A two-year prospective study. Journal of Neuroimmunology [Internet]. 2020;347(July):577328. Available from: https://doi.org/10.1016/j.jneuroim.2020.577328
17. Arce-Sillas A, Sevilla-Reyes E, Álvarez-Luquín DD, Guevara-Salinas A, Boll MC, Pérez-Correa CA, et al. Expression of Dopamine Receptors in Immune Regulatory Cells. NeuroImmunoModulation. 2019;26(3):159–65.
18. Pinoli M, Marino F, Cosentino M. Dopaminergic Regulation of Innate Immunity: a Review. Journal of Neuroimmune Pharmacology. 2017;12(4):602–23.
19. Cosentino M, Kustrimovic N, Ferrari M, Rasini E, Marino F. cAMP levels in lymphocytes and CD4(+) regulatory T-cell functions are affected by dopamine receptor gene polymorphisms. Immunology. 2018 Mar;153(3):337–41.
20. Kustrimovic N, Rasini E, Legnaro M, Marino F, Cosentino M. Expression of dopaminergic receptors on human CD4+ T lymphocytes: Flow cytometric analysis of naive and memory subsets and relevance for the neuroimmunology of neurodegenerative disease. Journal of Neuroimmune Pharmacology. 2014;9(3):302–12.
21. Cosentino M, Rasini E, Colombo C, Marino F, Blandini F, Ferrari M, et al. Dopaminergic modulation of oxidative stress and apoptosis in human peripheral blood lymphocytes: Evidence for a D1-like receptor-dependent protective effect. Free Radical Biology and Medicine. 2004;36(10):1233–40.
22. Kustrimovic N, Rasini E, Legnaro M, Bombelli R, Aleksic I, Blandini F, et al. Dopaminergic Receptors on CD4+ T Naive and Memory Lymphocytes Correlate with Motor Impairment in Patients with Parkinson’s Disease. Scientific Reports [Internet]. 2016;6(September):1–17. Available from: http://dx.doi.org/10.1038/srep33738

To cite this abstract in AMA style:

AY. Regalado-Mustafá, DD. álvarez-Luquín, A. Guevara-Salinas, MA. Bravo-Martinez, EJ. Gallegos-Altamirano, CF. álvarez-Hernández, E. Ichikawa-Escamilla, AM. Peralta-Maza, V. Morales-Ruiz, EE. Sevilla-Reyes, JI. Velasco-Velázquez, JE. Estudillo-Hernández, M. Rodríguez-Violante, LV. Adalid-Peralta. Functionality Analysis of Immunoregulatory Cells Stimulated with Dopaminergic Agonists in People Living with Parkinson’s Disease [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/functionality-analysis-of-immunoregulatory-cells-stimulated-with-dopaminergic-agonists-in-people-living-with-parkinsons-disease/. Accessed June 15, 2025.
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