TY - JOUR
T1 - Regulatory T cells attenuate Th17 cell-mediated nigrostriatal dopaminergic neurodegeneration in a model of Parkinson's disease
AU - Reynolds, Ashley D.
AU - Stone, David K.
AU - Hutter, Jessica A.L.
AU - Benner, Eric J.
AU - Mosley, R. Lee
AU - Gendelman, Howard E.
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/3/1
Y1 - 2010/3/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.0901852
DO - 10.4049/jimmunol.0901852
M3 - Article
C2 - 20118279
AN - SCOPUS:77951882307
SN - 0022-1767
VL - 184
SP - 2261
EP - 2271
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -