title: Neural precursors attenuate autoimmune encephalomyelitis by peripheral immunosuppression.
abstract: OBJECTIVE
  Intracerebroventricular or intravenous (IV) injection of neural precursor cells (NPCs) attenuates experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. Although stem cell therapy was introduced initially for cell replacement, we examine here whether NPCs possess immunomodulatory effects.
  
  
  METHODS
  We examined the effects of systemic administration of NPCs on central nervous system (CNS) inflammation in EAE and the interactions between NPCs and T cells in vitro and in vivo.
  
  
  RESULTS
  IV NPC therapy decreased significantly CNS inflammation and tissue injury and attenuated the clinical severity of EAE. IV-injected NPCs could not be found in the CNS but were detected in lymphoid organs. Coculture experiments showed that NPCs inhibited the activation and proliferation of lymph node-derived T cells in response to CNS-derived antigens and to nonspecific polyclonal stimuli. The relevance of NPC/lymph node cell interactions in vivo was further demonstrated when lymph node cells obtained from IV NPC-treated mice exhibited poor encephalitogenicity on transfer to naive mice and caused a markedly milder EAE compared with those obtained from nontreated mice.
  
  
  CONCLUSIONS
  IV administration of neural precursors inhibits EAE by a peripheral immunosuppressive effect. Our findings suggest a profound bystander inhibitory effect of NPCs on T-cell activation and proliferation in the lymph nodes, leading to amelioration of EAE.
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Ofira
authors.initials: O
authors.lastname: Einstein
authors.forename: Nina
authors.initials: N
authors.lastname: Fainstein
authors.forename: Ilan
authors.initials: I
authors.lastname: Vaknin
authors.forename: Rachel
authors.initials: R
authors.lastname: Mizrachi-Kol
authors.forename: Etti
authors.initials: E
authors.lastname: Reihartz
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Grigoriadis
authors.forename: Iris
authors.initials: I
authors.lastname: Lavon
authors.forename: Michal
authors.initials: M
authors.lastname: Baniyash
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Tamir
authors.initials: T
authors.lastname: Ben-Hur
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D007275:Injections, Intravenous; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D009474:Neurons / Q000166:cytology*; D010446:Peptide Fragments / Q000276:immunology; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)