Interleukin-2 expands neuroprotective regulatory T cells in Parkinson’s disease

BACKGROUND: Pharmacological approaches that boost neuroprotective regulatory T cell (Treg) number and function lead to neuroprotective activities in neurodegenerative disorders. OBJECTIVES: We investigated whether low-dose interleukin 2 (IL-2) expands Treg populations and protects nigrostriatal dopaminergic neurons in a model of Parkinson’s disease (PD). METHODS: IL-2 at 2.5 × 10(4) IU/dose/mouse was administered for 5 days. Lymphocytes were isolated and phenotype determined by flow cytometric analyses. To 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, 0.5 × 10(6) of enriched IL-2-induced Tregs were adoptively transferred to assess the effects on nigrostriatal neuron survival. RESULTS: IL-2 increased frequencies of CD4(+)CD25(+)CD127(low)FoxP3(+) Tregs that express ICOS and CD39 in blood and spleen. Adoptive transfer of IL-2-induced Tregs to MPTP-treated recipients increased tyrosine hydroxylase (TH)(+) nigral dopaminergic neuronal bodies by 51% and TH(+) striatal termini by 52% compared to control MPTP-treated animal controls. CONCLUSIONS: IL-2 expands numbers of neuroprotective Tregs providing a vehicle for neuroprotection of nigrostriatal dopaminergic neurons in a pre-clinical PD model.