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

Abstract

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 × 10⁴ 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 × 10⁶ 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^lowFoxP3⁺ 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.

Keywords: Parkinson’s disease; Tregs; immune tolerance; interleukin-2; neuroprotection; regulatory T cells.