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

Ashley D. Reynolds, David K. Stone, Jessica A L Hutter, Eric J. Benner, R Lee Mosley, Howard Eliot Gendelman

Research output: Contribution to journalArticle

207 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2261-2271
Number of pages11
JournalJournal of Immunology
Issue number5
StatePublished - Mar 1 2010


ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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