Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease

Abstract

Objective

To determine the activation status and cytokine profiles of CD4 ⁺ T cells, CD8 ⁺ T cells, and CD19 ⁺ B cells from patients with early-stage Parkinson disease (PD) compared with healthy controls (HCs).

Methods

Peripheral blood samples from 41 patients with early-stage PD and 40 HCs were evaluated. Peripheral blood mononuclear cells were analyzed by flow cytometry for surface markers and intracellular cytokine production. Correlations of immunologic changes and clinical parameters were analyzed.

Results

Adaptive immunity plays a role in the pathogenesis of PD, yet the contribution of T cells and B cells, especially cytokine production by these cells, is poorly understood. We demonstrate that naive CD4 ⁺ and naive CD8 ⁺ T cells are significantly decreased in patients with PD, whereas central memory CD4 ⁺ T cells are significantly increased in patients with PD. Furthermore, IL-17–producing CD4 ⁺ Th17 cells, IL-4–producing CD4 ⁺ Th2 cells, and IFN-γ–producing CD8 ⁺ T cells are significantly increased in patients with PD. Regarding B cells, we observed a decrease in naive B cells and an increase in nonswitched memory and double-negative B cells. As well, TNF-α–producing CD19 ⁺ B cells were significantly increased in patients with PD. Notably, some of the changes observed in CD4 ⁺ T cells and B cells were associated with clinical motor disease severity.

Conclusions

These findings suggest that alterations in the adaptive immune system may promote clinical disease in PD by skewing to a more proinflammatory state in the early-stage PD patient cohort. Our study may shed light on potential immunotherapies targeting dysregulated CD4 ⁺ T cells, CD8 ⁺ T cells, and CD19 ⁺ B cells in patients with PD.