T cells modulate disease associated neuroinflammation in Parkinson's disease (PD). We report that circulating CD4 + T cells from people with PD have a dysregulated transcriptional and cytokine response to fasting and refeeding and an altered metabolic profile. The CD4 + T cell secretome mediates a metabolic program in neurons that is impaired in PD, revealing dysfunctional neuro-immune signalling that may contribute to disease pathology.