Expression of Heme Oxygenase-1 in Neural Stem/Progenitor Cells as a Potential Mechanism to Evade Host Immune Response§

Authors

  • Virginie Bonnamain,

    1. INSERM, U643, Nantes, France
    2. CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France
    3. Université de Nantes, Faculté de Médecine, Nantes, France
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  • Elodie Mathieux,

    1. INSERM, U643, Nantes, France
    2. CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France
    3. Université de Nantes, Faculté de Médecine, Nantes, France
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  • Reynald Thinard,

    1. INSERM, U643, Nantes, France
    2. CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France
    3. Université de Nantes, Faculté de Médecine, Nantes, France
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  • PamÉla Thébault,

    1. INSERM, U643, Nantes, France
    2. CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France
    3. Université de Nantes, Faculté de Médecine, Nantes, France
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  • Véronique Nerrière-Daguin,

    1. INSERM, U643, Nantes, France
    2. CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France
    3. Université de Nantes, Faculté de Médecine, Nantes, France
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  • Xavier Lévêque,

    1. INSERM, U643, Nantes, France
    2. CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France
    3. Université de Nantes, Faculté de Médecine, Nantes, France
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  • Ignacio Anegon,

    1. INSERM, U643, Nantes, France
    2. CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France
    3. Université de Nantes, Faculté de Médecine, Nantes, France
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  • Bernard Vanhove,

    1. INSERM, U643, Nantes, France
    2. CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France
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  • Isabelle Neveu,

    1. INSERM, U643, Nantes, France
    2. CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France
    3. Université de Nantes, Faculté de Médecine, Nantes, France
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  • Philippe Naveilhan

    Corresponding author
    1. INSERM, U643, Nantes, France
    2. CHU de Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France
    3. Université de Nantes, Faculté de Médecine, Nantes, France
    • INSERM U643, 30 Bd Jean Monnet, 44 093 Nantes Cedex 01, France

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    • Telephone: +33-2-4008-7414; Fax: +33-2-4008-7411


  • Author contributions: V.B. and E.M.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; R.T., V.D.-N., and X.L.: collection and assembly of data; P.T., I.A., and B.V.: data analysis and interpretation; I.N. and P.N.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript. V.B., E.M., I.N., and P.N. contributed equally to this article.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS August 7, 2012.

Abstract

Besides their therapeutic benefit as cell source, neural stem/progenitor cells (NSPCs) exhibit immunosuppressive properties of great interest for modulating immune response in the central nervous system. To decipher the mechanisms of NSPC-mediated immunosuppression, activated T cells were exposed to NSPCs isolated from fetal rat brains. Analyses revealed that NSPCs inhibited T-cell proliferation and interferon-gamma production in a dose-dependent manner. A higher proportion of helper T cells (CD4+ T cells) was found in the presence of NSPCs, but analyses of FoxP3 population indicated that T-cell suppression was not secondary to an induction of suppressive regulatory T cells (FoxP3+ CD4+ CD25+). Conversely, induction of the high affinity interleukin-2 (IL-2) receptor (CD25) and the inability of IL-2 to rescue T-cell proliferation suggest that NSPCs display immunosuppressive activity without affecting T-cell activation. Cultures in Transwell chambers or addition of NSPC-conditioned medium to activated T cells indicated that part of the suppressive activity was not contact dependent. We therefore searched for soluble factors that mediate NSPC immunosuppression. We found that NSPCs express several immunosuppressive molecules, but the ability of these cells to inhibit T-cell proliferation was only counteracted by heme oxygenase (HO) inhibitors in association or not with nitric oxide synthase inhibitors. Taken together, our findings highlight a dynamic crosstalk between NSPCs and T lymphocytes and provide the first evidence of an implication of HO-1 in mediating the immunosuppressive effects of the NSPCs. STEM Cells2012;30:2342–2353

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