期刊
JOURNAL OF IMMUNOLOGY
卷 184, 期 5, 页码 2261-2271出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0901852
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资金
- Carol Swarts, M.D., Emerging Neuroscience Research Laboratory
- Frances and Louie Blumkin Foundation
- Community Neuroscience Pride of Nebraska Research Initiative
- Alan Baer Charitable Trust
- University of Nebraska Medical Center
- Michael J. Fox Foundation for Parkinson's Research
- National Institutes of Health [R21 NS049246, 5P01NS31492, 2R37NS36126, 2R01NS034239, P20RR15635, U54NS43011, P01MH64570, P01NS43985]
Nitrated alpha-synuclein (N-alpha-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-alpha-syn-induced T cells. In contrast, purified vasoactive intestinal peptide induced and natural Tregs reversed N-alpha-syn T cell nigrostriatal degeneration. Combinations of adoptively transferred N-alpha-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-alpha-syn-induced neurodestructive immunity and, as such, provide a sound rationale for future Parkinson's disease immunization strategies. The Journal of Immunology, 2010,184: 2261-2271.
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