Neuroprotection by IL-10-producing MOG CD4+ T cells following ischemic stroke

Dan Frenkel, Zhihong Huang, Ruth Maron, Djordje N. Koldzic, Michael A. Moskowitz, Howard L. Weiner

Research output: Contribution to journalArticlepeer-review

Abstract

Mucosal tolerance has been used successfully to treat animal models of autoimmune diseases and is being tested in human diseases. In this work we demonstrate the reduction of infarct size following mucosal tolerance by myelin oligodendrocyte glycoprotein (MOG) (35-55) peptide in mouse stroke model. Nasal MOG was most efficacious and reduced ischemic infarct size by 70% at 24 h as well as improving behavior score. Using immunohistological methods and IL-10 -/- mice, we demonstrate the importance of IL-10-producing CD4+ T cells in the reduction of the ischemic infarct volume following middle cerebral artery occlusion (MCAO). Furthermore, adoptive transfer of CD4+ T cells from nasally tolerized mice to untreated mice prior to MCAO surgery significantly decreased stroke size (p < 0.001 vs. control), whereas CD4+ T cells from nasally tolerized IL-10-deficient mice had no significant effect. Based on these results, modulation of cerebral inflammation by mucosal tolerance to myelin antigens may have applicability both as prophylactic therapy and treatment following ischemia attacks.

Original languageEnglish
Pages (from-to)125-132
Number of pages8
JournalJournal of the Neurological Sciences
Volume233
Issue number1-2
DOIs
StatePublished - 15 Jun 2005
Externally publishedYes

Keywords

  • IL-10
  • Mucosa
  • Myelin oligodendrocyte glycoprotein
  • Stroke
  • T cells
  • Tolerance

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