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Antigen-specific adaptive immunity in Parkinson's disease: peripheral priming, brain-border reactivation and parenchymal injury.

Created on 26 Jun 2026

Authors

Kehao Wang, Ke Han, Yanqing Wang

Published in

Journal of neuroinflammation. Jun 26, 2026. Epub Jun 26, 2026.

Abstract

Adaptive immune signals in Parkinson's disease (PD) now extend beyond descriptive neuroinflammation. Human genetic studies have implicated HLA variation, peripheral assays have detected α-synuclein- and PINK1-reactive T cells, neuropathology has identified early nigral CD8 + T-cell accumulation, and PD-relevant models have linked α-synuclein or mitochondrial antigen presentation to defined T-cell programs. This Review first places these findings in the modifying context of aging and then examines two antigen-specific routes across peripheral T-cell priming, central nervous system (CNS)-border reactivation or retention, and parenchymal effector injury. The α-synuclein/HLA-II/CD4 + T-cell route has the clearest support from human T-cell reactivity and border-associated macrophage (BAM)-dependent antigen presentation. The mitochondrial antigen/MHC-I/CD8 + T-cell route is strongest in PINK1-Parkin dysfunction and inflammatory settings, including CD8 + T-cell-mediated killing of Pink1 - / - dopaminergic neurons after mitochondrial antigen presentation. Trafficking mechanisms drawn from experimental autoimmune encephalomyelitis (EAE), multiple sclerosis (MS), viral encephalitis and cerebral malaria provide useful candidate pathways for PD studies, especially for post-vascular retention and glia-limitans passage. We also consider viral antigens as potential contributors to resident-memory-like CD8 + T-cell pools in the brain and discuss why PD models should be selected according to antigen axis, T-cell subset and immune context.

PMID:
42351163
Bibliographic data and abstract were imported from PubMed on 26 Jun 2026.

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