Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease

Ashley D. Reynolds, Rebecca Banerjee, Jianou Liu, Howard Eliot Gendelman, R Lee Mosley

Research output: Contribution to journalArticle

202 Citations (Scopus)

Abstract

Progressive loss of dopaminergic neurons in the substantia nigra pars compacta and their terminal connections in the striatum are central features in Parkinson's disease (PD). Emerging evidence supports the notion that microglia neuroinflammatory responses speed neurodegenerative events. We demonstrated previously that this can be slowed by adoptive transfer of T cells from Copolymer-1-immunized mice administered to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) recipients. The cellular basis for this neuroprotective response was the CD4+ T cell population, suggesting involvement of CD4+CD25+ regulatory T cells (Tregs), cells known to suppress immune activation and maintain immune homeostasis and tolerance. We show for the first time that adoptive transfer of CD3-activated Tregs to MPTP-intoxicated mice provides greater than 90% protection of the nigrostriatal system. The response was dose-dependent and paralleled modulation of microglial responses and up-regulation of glial cell-derived neurotrophic factor (CDNF) and TGF-β. Interestingly, that adoptive transfer of effector T cells showed no significant neuroprotective activities. Tregs were found to mediate neuroprotection through suppression of microglial responses to stimuli, including aggregated, nitrated α-synuclein. Moreover, Treg-mediated suppression was also operative following removal of Tregs from culture prior to stimulation. This neuroprotection was achieved through modulation of microglial oxidative stress and inflammation. As Tregs can be modulated in vivo, these data strongly support the use of such immunomodulatory strategies to treat PD.

Original languageEnglish (US)
Pages (from-to)1083-1094
Number of pages12
JournalJournal of Leukocyte Biology
Volume82
Issue number5
DOIs
StatePublished - Nov 1 2007

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Adoptive Transfer
Regulatory T-Lymphocytes
Parkinson Disease
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animal Models
T-Lymphocytes
Synucleins
Immune Tolerance
Dopaminergic Neurons
Nerve Growth Factors
Microglia
Neuroglia
Oxidative Stress
Homeostasis
Up-Regulation
Inflammation
Population
Neuroprotection

Keywords

  • Inflammation
  • Microglia
  • Neurodegeneration
  • Neuroprotection

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease. / Reynolds, Ashley D.; Banerjee, Rebecca; Liu, Jianou; Gendelman, Howard Eliot; Mosley, R Lee.

In: Journal of Leukocyte Biology, Vol. 82, No. 5, 01.11.2007, p. 1083-1094.

Research output: Contribution to journalArticle

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