title: Neuroprotection by IL-10-producing MOG CD4+ T cells following ischemic stroke.
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.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Frenkel
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Huang
authors.forename: Ruth
authors.initials: R
authors.lastname: Maron
authors.forename: Djordje N
authors.initials: DN
authors.lastname: Koldzic
authors.forename: Michael A
authors.initials: MA
authors.lastname: Moskowitz
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001522:Behavior, Animal; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage*; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D016753:Interleukin-10 / Q000172:deficiency / Q000378:metabolism* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage*; D012720:Severity of Illness Index; D020521:Stroke / Q000209:etiology / Q000628:therapy*; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D016753:Interleukin-10