Interleukin-2 expands neuroprotective regulatory T cells in Parkinson’s disease
Milica Marković, Pravin Yeapuri, Krista L. Namminga, Yaman Lu, Maamoon Saleh, Katherine E. Olson, Howard E. Gendelman, R. Lee Mosley
Abstract
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 × 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.