Regulatory T cells attenuate Th17 cell-mediated nigrostriatal dopaminergic neurodegeneration in a model of Parkinson's disease.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Reynolds, AD; Stone, DK; Hutter, JAL; Benner, EJ; Mosley, RL; Gendelman, HE

Published Date

  • March 1, 2010

Published In

Volume / Issue

  • 184 / 5

Start / End Page

  • 2261 - 2271

PubMed ID

  • 20118279

Pubmed Central ID

  • PMC2824790

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.0901852


  • eng

Conference Location

  • United States