T Lymphocytes in Parkinson's Disease

Abstract

T cells are key mediators of both humoral and cellular adaptive immune responses, and their role in Parkinson's disease (PD) is being increasingly recognized. Several lines of evidence have highlighted how T cells are involved in both the central nervous system and the periphery, leading to a profound imbalance in the immune network in PD patients. This review discusses the involvement of T cells in both preclinical and clinical studies, their importance as feasible biomarkers of motor and non-motor progression of the disease, and recent therapeutic strategies addressing the modulation of T cell response.

Keywords: CD4 + T cells; CD8 + T cells; Parkinson’s disease; T cells; neuroinflammation; peripheral immunity.

Fig. 1

Central and peripheral involvement of T cells in PD. Naïve CD4 + and CD8 + T lymphocytes are activated in the periphery after the interaction with antigen-presenting cells. CD4 + T cells then differentiate into pro-inflammatory (Th1, Th17) or anti-inflammatory (Th2, Treg) subtypes, characterized by the release of specific patterns of cytokines. Activated T cells can reach the central nervous system by crossing an altered blood-brain barrier, thus polarizing resident cells to pro-inflammatory or anti-inflammatory phenotypes. In particular, Th1 and Th17 subsets release pro-inflammatory molecules (TNF-α, IFN-γ, IL-17, IL-21, IL-22), which, in concert with other mechanisms, lead to neuronal damage and death. Detrimental pro-inflammatory pathways are indicated with red lines. Figure created with BioRender.com.