CD4⁺ T cells mediate cytotoxicity in neurodegenerative diseases

Neuroinflammation, characterized by activated microglia and infiltrating T cells, is a prominent pathological feature in neurodegenerative diseases. However, whether this inflammation contributes to neuronal injury or is a late consequence of neuronal injury is unclear. In this issue of the JCI, Brochard et al. report that CD4⁺ T cells are cytotoxic in a mouse model of Parkinson disease (PD) (see the related article beginning on page 182). Specifically, invading T lymphocytes contributed to neuronal cell death via the Fas/FasL pathway. The results implicate the adaptive immune system in the pathogenesis of Parkinson neurodegeneration and provide a meaningful rationale for immune-based therapies for PD.