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

Abstract

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.

Changes of T lymphocyte subpopulations and their roles in predicting the risk of Parkinson’s disease

“…Compared to HC, PD patients showed a consistent decline of CD8 + Tn cells, which was also independent of the therapeutic agents. This result was in agreement with the latest studies performed in the United States and Mexico separately [ 38 , 39 ], suggesting the consistent changes of CD8 + Tn cells in PD among different races. As the proliferation of naïve T cells and their differentiation into memory T cells are related to cellular senescence [ 40 ], the decrease of CD8 + Tn cells may reflect abnormal aging in PD patients.…”

Lymphocyte Count and Neutrophil-to-Lymphocyte Ratio Are Associated with Mild Cognitive Impairment in Parkinson’s Disease: A Single-Center Longitudinal Study

“…The NLR was calculated as absolute neutrophil count divided by absolute lymphocyte count. All patients were in the drug-naïve condition to exclude potential effects of anti-Parkinsonian treatment on the immunological profile [ 15 , 16 ]. At the time of enrollment, clinical examination was performed by neurologists with experience in movement disorders, and motor symptoms were assessed by using the Unified Parkinson’s Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr (HY) scale [ 17 , 18 ].…”

T Lymphocytes in Parkinson’s Disease

“…Similarly, Chen et al found a weak association between the percentage of CD4 + T cells and the levodopa equivalent daily dose [ 24 ]. In another study [ 45 ], the negative correlation between the levels of T cytotoxic cells 1 (CD8 + Tbet+IFN- γ +) and T cytotoxic cells 2 (CD8 + GATA3 + IL-13+) with the Hoehn and Yahr scale score was observed only in patients receiving treatment with levodopa, thus suggesting that levodopa could affect T cytotoxic cells. Furthermore, it should be noticed that human and murine lymphocytes express all the five subtypes of DR, and the DRD2 agonist sumanirole was able to inhibit the shift to the Th1 and Th17 phenotypes of CD4 + T cells obtained from MPTP-intoxicated mice [ 46 ].…”