• Open Access

Neural progenitors derived from human embryonic stem cells are targeted by allogeneic T and natural killer cells

Authors

  • Olivier Preynat-Seauve,

    1. Laboratory of Experimental Cell Therapy, Department of Genetic and Laboratory Medicine, Geneva University Hospital, Switzerland
    2. Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Switzerland
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    • These authors contributed equally to this work.

  • Casimir de Rham,

    1. Immunology and Transplant Unit, Division of Immunology and Allergology and Division of Laboratory Medicine, Geneva University Hospital and Medical School, Switzerland
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    • These authors contributed equally to this work.

  • Diderik Tirefort,

    1. Laboratory of Experimental Cell Therapy, Department of Genetic and Laboratory Medicine, Geneva University Hospital, Switzerland
    2. Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Switzerland
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  • Sylvie Ferrari-Lacraz,

    1. Immunology and Transplant Unit, Division of Immunology and Allergology and Division of Laboratory Medicine, Geneva University Hospital and Medical School, Switzerland
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  • Karl-Heinz Krause,

    1. Laboratory of Experimental Cell Therapy, Department of Genetic and Laboratory Medicine, Geneva University Hospital, Switzerland
    2. Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Switzerland
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  • Jean Villard

    Corresponding author
    1. Immunology and Transplant Unit, Division of Immunology and Allergology and Division of Laboratory Medicine, Geneva University Hospital and Medical School, Switzerland
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Correspondence to: Jean VILLARD, M.D., Ph.D., Immunology and Transplant Unit, Geneva University Hospital and Medical School, 24, rue Micheli-du-Crest 1211 Geneva 14, Switzerland.
Tel.: +4122 3729394
Fax: +4122 3729390
E-mail: Jean.Villard@hcuge.ch

Abstract

Neural progenitor cells (NPC) of foetal origin or derived from human embryonic stem cells (HESC) have the potential to differentiate into mature neurons after transplantation into the central nervous system, opening the possibility of cell therapy for neurodegenerative disorders. In most cases, the transplanted NPC are genetically unrelated to the recipient, leading to potential rejection of the transplanted cells. Very few data provide reliable information as to the potential immune response of allogeneic neural progenitors derived from HESC. In this study, we analyzed in vitro the allogeneic immune response of T lymphocytes and natural killer (NK) cells to NPC derived from HESC or of foetal origin. We demonstrate that NPC induce T-cell stimulation and a strong NK cytotoxic response. NK-cell activity is unrelated to MHC-I expression but driven by the activating NKG2D receptor. Cyclosporine and dexamethasone previously used in clinical studies with foetal NPC did not only fail to prevent NK alloreactivity but strongly inhibited the terminal maturation from NPC into mature neurons. We conclude that allogenic transplantation of NPC in the central nervous system will most likely require an immunosuppressive regimen targeting allogenic T and NK cells, whereas possible interference with the differentiation of NPC needs to be carefully evaluated.

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