Regulatory T Cells Attenuate Th17 Cell-Mediated Nigrostriatal Dopaminergic Neurodegeneration in a Model of Parkinson’s Disease
Open Access
- 1 March 2010
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 184 (5), 2261-2271
- https://doi.org/10.4049/jimmunol.0901852
Abstract
Nitrated α-synuclein (N–α-syn) immunization elicits adaptive immune responses to novel antigenic epitopes that exacerbate neuroinflammation and nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson’s disease. We show that such neuroimmune degenerative activities, in significant measure, are Th17 cell-mediated, with CD4+CD25+ regulatory T cell (Treg) dysfunction seen among populations of N–α-syn–induced T cells. In contrast, purified vasoactive intestinal peptide induced and natural Tregs reversed N–α-syn T cell nigrostriatal degeneration. Combinations of adoptively transferred N–α-syn and vasoactive intestinal peptide immunocytes or natural Tregs administered to MPTP mice attenuated microglial inflammatory responses and led to robust nigrostriatal protection. Taken together, these results demonstrate Treg control of N–α-syn–induced neurodestructive immunity and, as such, provide a sound rationale for future Parkinson’s disease immunization strategies.Keywords
This publication has 37 references indexed in Scilit:
- Proteomic Studies of Nitrated Alpha-Synuclein Microglia Regulation by CD4+CD25+ T CellsJournal of Proteome Research, 2009
- Nitrated α-Synuclein-Induced Alterations in Microglial Immunity Are Regulated by CD4+ T Cell SubsetsThe Journal of Immunology, 2009
- Neuromodulatory Activities of CD4+CD25+ Regulatory T Cells in a Murine Model of HIV-1-Associated NeurodegenerationThe Journal of Immunology, 2009
- Targeted Overexpression of Human α-Synuclein Triggers Microglial Activation and an Adaptive Immune Response in a Mouse Model of Parkinson DiseaseJournal of Neuropathology and Experimental Neurology, 2008
- IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+regulatory T cellsProceedings of the National Academy of Sciences of the United States of America, 2008
- Adaptive Immune Neuroprotection in G93A-SOD1 Amyotrophic Lateral Sclerosis MicePLOS ONE, 2008
- Induction of Immunologic Tolerance to Myelin Basic Protein Prevents Central Nervous System Autoimmunity and Improves Outcome After StrokeStroke, 2008
- Immunological decision‐making: how does the immune system decide to mount a helper T‐cell response?Immunology, 2008
- Nitrated α–Synuclein Immunity Accelerates Degeneration of Nigral Dopaminergic NeuronsPLOS ONE, 2008
- CD4+CD25+Foxp3+regulatory T cells induce alternative activation of human monocytes/macrophagesProceedings of the National Academy of Sciences of the United States of America, 2007