Increased Tc17 cell levels and imbalance of naïve/effector immune response in Parkinson's disease patients in a two-year follow-up: a case control study.

BACKGROUND: Neuroinflammation has been proved to play a role in dopaminergic neuronal death in Parkinson's disease (PD). This link highlights the relevance of the immune response in the progression of the disease. However, little is known about the impact of peripheral immune response on the disease. This study is aimed to evaluate how immune cell populations change in untreated PD patients followed-up for 2 years. METHODS: Thirty-two patients with no previous treatment (PD-0 yr) and twenty-two healthy subjects (controls) were included in the study. PD patients were sampled 1 and 2 years after the start of the treatment. CD4 T cells (naïve/central memory, effector, and activated), CD8 T cells (activated, central memory, effector memory, NKT, Tc1, Tc2, and Tc17), and B cells (activated, plasma, and Lip-AP) were characterized by flow cytometry. RESULTS: We observed decreased levels of naïve/central memory CD4 and CD8 T cells, Tc1, Tc2, NKT, and plasma cells, and increased levels of effector T cells, activated T cells, and Tc17. CONCLUSIONS: PD patients treated for 2 years showed an imbalance in the naive/effector immune response. Naïve and effector cell levels were associated with clinical deterioration. These populations are also correlated to aging. On the other hand, higher Tc17 levels suggest an increased inflammatory response, which may impact the progression of the disease. Our results highlight the relevant effect of treatment on the immune response, which could improve our management of the disease.

Immunomodulatory effect and clinical outcome in Parkinson's disease patients on levodopa-pramipexole combo therapy: A two-year prospective study.

Parkinson's disease (PD), the second most frequent neurodegenerative disease, has been linked to increased central and peripheral inflammation. Although the response of the immune system to dopaminergic treatment remains to be fully understood, dopaminergic agonists are known to exhibit immunoregulatory properties which may, at least in part, explain their therapeutic effect in PD. This highlights the need of analyzing immune parameters in longitudinal studies on PD patients receiving specific therapeutic regimes. In this work, PD patients were included in a two-year prospective study comparing the effect of levodopa alone and a levodopa/pramipexole combo therapy on several regulatory and pro-inflammatory immune cell populations. We demonstrated that PD patients show decreased circulating levels of several important regulatory subpopulations, as determined by flow cytometry. Notably, when administered alone, levodopa decreased the levels of functional Bregs and SLAMF1+ tolerogenic DCs and increased the levels of total and HLA-DR+ classical monocytes, while the pramipexole/levodopa combo may promote Treg- and tolerogenic DC-mediated regulatory responses. These results suggest that a regime based on levodopa alone may promote a pro-inflammatory-type response in PD patients, but when combined with pramipexole, it promotes a clinically beneficial regulatory-type environment.