The following is a summary of “Early-to-mid stage idiopathic Parkinson’s disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females,” published in the November 2023 issue of Neurology by Capelle et al.

While neuroinflammation within the brain significantly contributes to Parkinson’s disease (PD) pathogenesis, the potential dysregulation of peripheral immunity in idiopathic PD (IPD) has not undergone systematic investigation. The study aimed to delineate alterations in peripheral immune profiles associated with early-to-mid-stage iPD, particularly focusing on gender-specific variations. Their analysis of over 700 innate and adaptive immune features revealed an elevated cytotoxic immune milieu in fresh blood samples from patients with early-to-mid iPD, particularly prominent among females. Notably, this immune profile showcased an abundance of terminally-differentiated effector memory (TEMRA) CD8 T cells, CD8+ NKT cells, and elevated levels of circulating cytotoxic molecules. 

Furthermore, a reduced count of CD8⁺FOXP3⁺ T cells corroborated this cytotoxic immune milieu, a pattern validated within another subcohort. Importantly, their findings unveiled enhanced co-expression of cytotoxic molecules, specifically within CD8 TEMRA and effector memory (TEM) cells. Leveraging single-cell RNA-sequencing analysis, the researchers demonstrated accelerated differentiation within CD8 compartments, with heightened cytotoxic pathways discerned in CD8 TEMRA and TEM cells. Intriguingly, even CD8 central memory (TCM) and naïve cells exhibited increased activity and transcriptional reprogramming.

This comprehensive exploration unravels a map of dysregulated peripheral immunity in iPD, shedding light on potential candidates crucial for early diagnosis and targeted therapeutic interventions. The observed alterations in immune profiles, especially the prominence of cytotoxic immune elements, offer insights into the pathological immune landscape of iPD, thereby paving the way for prospective diagnostic and treatment strategies.

Source: nature.com/articles/s41467-023-43053-0