Inflammation is implicated as a major pathogenic factor in the onset and progression of Parkinson’s Disease (PD), the most common neurodegenerative movement disorder. Cells of the innate and adaptive immune system are involved in PD, including microglia, infiltrating macrophages and T-cells, with characterization of abundant production of cytokines.In our current studies, we focused on comparing adaptive and innate immune cells in peripheral blood of PD patients and healthy controls (HCs) with assessment by extensive flow cytometry analysis. Our results demonstrate that immunologic abnormalities are mainly in CD4+ T-cell populations in patients with PD, with some observed sex differences. For CD4+ T-cells, we observed a significant decrease of naïve CD4+ T-cells in PD patients, while central memory CD4+ T-cells are increased in male PD patients, suggesting an activational phenotype of CD4+ T-cells. With respect to CD4+ T-cell subsets, there is an increase in Th17 cells producing IL-17A in PD patients, especially males, while there was an increase in Th2 cells producing IL-4, prominently in female PD patients. Surprisingly, IFN-g-induced STAT1 and IL-6-induced STAT3 activation were diminished in CD4+ T-cells from PD patients compared HCs. These changes are related to clinical disease severity, specifically with MDS-UPRS scores and Schwab and England scores. The types and numbers of medication had no influence on immune cell phenotypes. Dysregulated adaptive CD4+ phenotypical profiles and JAK/STAT activation may contribute to the development of PD, and may serve as potential biomarkers and targets for novel immunomodulating therapeutics in PD patients.