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Reduced Activated T Lymphocytes (CD4+CD25+) and Plasma Levels of Cytokines in Parkinson’s Disease

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Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease. The cause of neurodegeneration in PD is not completely understood, and evidence has shown that inflammatory/immune changes may be involved in PD pathophysiology. Herein, we aimed to determine the profile of the peripheral immune system in patients with PD in comparison with controls. Forty patients with PD and 25 age- and gender-matched controls were enrolled in this study. From these, 23 PD patients and 21 controls were included in the immunophenotyping analyses. Peripheral blood was drawn on the same day of the clinical assessment and submitted to plasma separation for enzyme-linked immunosorbent assay or cytometric bead array. Immunophenotyping analyses of the peripheral blood were performed by flow cytometry. We found that patients with PD presented peripheral immune changes evidenced by decreased percentage of T lymphocytes (CD3+ cells), especially activated T lymphocytes (CD4+CD25+ cells), when compared with controls. In line with these results, we also found decreased plasma levels of the cytokines IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17A in the PD group. In vitro experiments demonstrated that the production of cytokines by peripheral blood mononuclear cells harvested from healthy young donors was reduced after exposure to the anti-parkinsonian drugs levodopa and pramipexole. Our data corroborate the hypothesis that immunological mechanisms are involved in PD. It is not clear whether the differences that we have found are due to adaptive mechanisms or to changes associated with PD, including pharmacological treatment, or even directly related to the disease pathophysiology. Future studies are needed in this regard.

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References

  1. Samii A, Nutt JG, Ransom BR (2004) Parkinson’s disease. Lancet 363(9423):1783–1793. doi:10.1016/S0140-6736(04)16305-8

    Article  CAS  PubMed  Google Scholar 

  2. Jain S, Goldstein DS (2012) What are Parkinson disease? Non-motor features transform conception of the shaking palsy. Neurobiol Dis 46(3):505–507. doi:10.1016/j.nbd.2012.04.013

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bekris LM, Mata IF, Zabetian CP (2010) The genetics of Parkinson disease. J Geriatr Psychiatry Neurol 23(4):228–242. doi:10.1177/0891988710383572

    Article  PubMed  PubMed Central  Google Scholar 

  4. Collins LM, Toulouse A, Connor TJ, Nolan YM (2012) Contributions of central and systemic inflammation to the pathophysiology of Parkinson’s disease. Neuropharmacology 62(7):2154–2168. doi:10.1016/j.neuropharm.2012.01.028

    Article  CAS  PubMed  Google Scholar 

  5. Bas J, Calopa M, Mestre M, Mollevi DG, Cutillas B, Ambrosio S, Buendia E (2001) Lymphocyte populations in Parkinson’s disease and in rat models of parkinsonism. J Neuroimmunol 113(1):146–152

    Article  CAS  PubMed  Google Scholar 

  6. Baba Y, Kuroiwa A, Uitti RJ, Wszolek ZK, Yamada T (2005) Alterations of T-lymphocyte populations in Parkinson disease. Parkinsonism Relat Disord 11(8):493–498. doi:10.1016/j.parkreldis.2005.07.005

    Article  PubMed  Google Scholar 

  7. Katsarou Z, Bostantjopoulou S, Hatzizisi O, Giza E, Soler-Cardona A, Kyriazis G (2007) Immune factors or depression? Fatigue correlates in Parkinson’s disease. Rev Neurol 45(12):725–728

    CAS  PubMed  Google Scholar 

  8. Niwa F, Kuriyama N, Nakagawa M, Imanishi J (2012) Effects of peripheral lymphocyte subpopulations and the clinical correlation with Parkinson’s disease. Geriatr Gerontol Int 12(1):102–107. doi:10.1111/j.1447-0594.2011.00740.x

    Article  PubMed  Google Scholar 

  9. Saunders JA, Estes KA, Kosloski LM, Allen HE, Dempsey KM, Torres-Russotto DR, Meza JL, Santamaria PM et al (2012) CD4+ regulatory and effector/memory T cell subsets profile motor dysfunction in Parkinson’s disease. J NeuroImmune Pharmacol 7(4):927–938. doi:10.1007/s11481-012-9402-z

    Article  PubMed  PubMed Central  Google Scholar 

  10. Stevens CH, Rowe D, Morel-Kopp MC, Orr C, Russell T, Ranola M, Ward C, Halliday GM (2012) Reduced T helper and B lymphocytes in Parkinson’s disease. J Neuroimmunol 252(1–2):95–99. doi:10.1016/j.jneuroim.2012.07.015

    Article  CAS  PubMed  Google Scholar 

  11. Kluter H, Vieregge P, Stolze H, Kirchner H (1995) Defective production of interleukin-2 in patients with idiopathic Parkinson’s disease. J Neurol Sci 133(1–2):134–139

    Article  CAS  PubMed  Google Scholar 

  12. Bessler H, Djaldetti R, Salman H, Bergman M, Djaldetti M (1999) IL-1 beta, IL-2, IL-6 and TNF-alpha production by peripheral blood mononuclear cells from patients with Parkinson’s disease. Biomed Pharmacother 53(3):141–145. doi:10.1016/S0753-3322(99)80079-1

    Article  CAS  PubMed  Google Scholar 

  13. Wandinger KP, Hagenah JM, Kluter H, Rothermundt M, Peters M, Vieregge P (1999) Effects of amantadine treatment on in vitro production of interleukin-2 in de-novo patients with idiopathic Parkinson’s disease. J Neuroimmunol 98(2):214–220

    Article  CAS  PubMed  Google Scholar 

  14. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55(3):181–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fahn S, Elton R (1987) Unified Parkinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Caine DB, Goldstein M (eds) Recent developments in Parkinson’s disease, vol 2. Macmillan Health Care Information, Florham Park, NJ, pp. 153–163 293–304

    Google Scholar 

  16. Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17(5):427–442

    Article  CAS  PubMed  Google Scholar 

  17. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–198

    Article  CAS  PubMed  Google Scholar 

  18. Dubois B, Slachevsky A, Litvan I, Pillon B (2000) The FAB: a Frontal Assessment Battery at bedside. Neurology 55(11):1621–1626

    Article  CAS  PubMed  Google Scholar 

  19. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571

    Article  CAS  PubMed  Google Scholar 

  20. Hurny A, Michalowska-Wender G, Wender M (2013) Impact of L-DOPA treatment of patients with Parkinson’s disease on mononuclear subsets and phagocytosis in the peripheral blood. Folia Neuropathol 51(2):127–131

    Article  CAS  PubMed  Google Scholar 

  21. Hasegawa Y, Inagaki T, Sawada M, Suzumura A (2000) Impaired cytokine production by peripheral blood mononuclear cells and monocytes/macrophages in Parkinson’s disease. Acta Neurol Scand 101(3):159–164

    Article  CAS  PubMed  Google Scholar 

  22. Tribl GG, Wober C, Schonborn V, Brucke T, Deecke L, Panzer S (2001) Amantadine in Parkinson’s disease: lymphocyte subsets and IL-2 secreting T cell precursor frequencies. Exp Gerontol 36(10):1761–1771

    Article  CAS  PubMed  Google Scholar 

  23. Alberio T, Pippione AC, Comi C, Olgiati S, Cecconi D, Zibetti M, Lopiano L, Fasano M (2012) Dopaminergic therapies modulate the T-CELL proteome of patients with Parkinson’s disease. IUBMB Life 64(10):846–852. doi:10.1002/iub.1073

    Article  CAS  PubMed  Google Scholar 

  24. Striz I, Brabcova E, Kolesar L, Sekerkova A (2014) Cytokine networking of innate immunity cells: a potential target of therapy. Clin Sci (Lond) 126(9):593–612. doi:10.1042/CS20130497

    Article  CAS  Google Scholar 

  25. Pessoa Rocha N, Reis HJ, Vanden Berghe P, Cirillo C (2014) Depression and cognitive impairment in Parkinson’s disease: a role for inflammation and immunomodulation. Neuroimmunomodulation 21(2–3):88–94. doi:10.1159/000356531

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors would like to acknowledge the participation of volunteers in this study and are indebted to their caregivers for their magnificent support. They also would like to thank Ilma Marҫal Souza for her skilled technical assistance, professor Mauro Martins Teixeira (Universidade Federal de Minas Gerais) for his support in the execution of this work, and Flavia Bastos and Andre Paiva for providing the drugs we used in this study. This study was funded by FAPEMIG, CNPq, and CAPES.

Authors’ Contributions

NPR, ALT, and HJR worked on the conception and organization of the research project. NPR, FA, ELMV, PLS, IGB, MSS, and PPC worked on the execution of the research project. NPR and ALT designed and executed the statistical analyses and wrote the first draft of the manuscript. HJR and ALT reviewed the statistical analyses and the manuscript. All authors read and approved the final manuscript.

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Correspondence to Natalia Pessoa Rocha.

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Ethics Approval and Consent to Participate

All subjects provided written informed consent before admission to the study. The Research Ethics Committee of the Universidade Federal de Minas Gerais, Brazil, approved this study (reference number CAAE-0417.0.203.000-11).

Competing Interests

The authors declare that they have no competing interests.

Funding

Funding for this study was provided by FAPEMIG, CNPq, and CAPES, Brazilian government research-funding agencies. NPR and ELMV are currently CNPq and FAPEMIG fellowship recipients, respectively. ALT and HJR are CNPq fellowship recipients.

Additional information

Helton José Reis and Antonio Lucio Teixeira contributed equally to the study.

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Rocha, N.P., Assis, F., Scalzo, P.L. et al. Reduced Activated T Lymphocytes (CD4+CD25+) and Plasma Levels of Cytokines in Parkinson’s Disease. Mol Neurobiol 55, 1488–1497 (2018). https://doi.org/10.1007/s12035-017-0404-y

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  • DOI: https://doi.org/10.1007/s12035-017-0404-y

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