Milica Markovic, Pravin Yeapuri, Krista L Namminga, Yaman Lu, Maamoon Saleh, Katherine E Olson, Howard E Gendelman, R Lee Mosley
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引用次数: 0
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+CD127lowFoxP3+ 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.
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