Get access

Neural precursors attenuate autoimmune encephalomyelitis by peripheral immunosuppression

Authors

  • Ofira Einstein MSc,

    1. Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah–Hebrew University Medical Center, Israel
    Search for more papers by this author
  • Nina Fainstein BSC,

    1. Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah–Hebrew University Medical Center, Israel
    Search for more papers by this author
  • Ilan Vaknin MSc,

    1. The Lautenberg Center for General and Tumor Immunology, Hebrew University, Jerusalem, Israel
    Search for more papers by this author
  • Rachel Mizrachi-Kol,

    1. Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah–Hebrew University Medical Center, Israel
    Search for more papers by this author
  • Etti Reihartz,

    1. Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah–Hebrew University Medical Center, Israel
    Search for more papers by this author
  • Nikolaos Grigoriadis MD, PhD,

    1. B‘Department of Neurology, American Hellenic Educational Progressive Association University Hospital of Thessaloniki, Greece
    Search for more papers by this author
  • Iris Lavon PhD,

    1. Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah–Hebrew University Medical Center, Israel
    2. Leslie and Michael Gaffin Center for Neuro-Oncology, Hadassah–Hebrew University Medical Center, Jerusalem, Israel
    Search for more papers by this author
  • Michal Baniyash PhD,

    1. The Lautenberg Center for General and Tumor Immunology, Hebrew University, Jerusalem, Israel
    Search for more papers by this author
  • Hans Lassmann MD, PhD,

    1. Center for Brain Research, Medical University of Vienna, Vienna, Austria
    Search for more papers by this author
  • Tamir Ben-Hur MD, PhD

    Corresponding author
    1. Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah–Hebrew University Medical Center, Israel
    • Department of Neurology, Hadassah Hebrew University Medical Center, Ein-Kerem, PO Box 12,000, Jerusalem 91120, Israel
    Search for more papers by this author

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.

Interpretation

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. Ann Neurol 2006

Ancillary