Reciprocal Interactions Between Human Mesenchymal Stem Cells and γδ T Cells Or Invariant Natural Killer T Cells§

Authors

  • Ignazia Prigione,

    Corresponding author
    1. Laboratory of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genoa, Italy
    • Laboratorio Scientifico di Oncologia, IRCCS G. Gaslini, Largo G. Gaslini 5, 16148 Genoa, Italy

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    • Telephone: 39 010 5636342; Fax: 39 010 3779820

  • Federica Benvenuto,

    1. Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy
    2. Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy
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  • Paola Bocca,

    1. Laboratory of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genoa, Italy
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  • Luca Battistini,

    1. Neuroimmunology Unit, European Centre for Brain Research, Santa Lucia Foundation, Rome, Italy
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  • Antonio Uccelli,

    1. Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy
    2. Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy
    3. Advanced Biotechnology Center, Genoa, Italy
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  • Vito Pistoia

    1. Laboratory of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genoa, Italy
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  • Author contributions: I.P. and F.B.: conception and design, collection of data, data analysis and interpretation, manuscript writing; P.B.: collection of data; L.B.: conception and design, data analysis and interpretation; A.U. and V.P.: conception and design, data analysis and interpretation, manuscript writing, financial support. I.P. and F.B. contributed equally as first authors to this work. A.U. and V.P. contributed equally as last authors to this work.

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

  • §

    First published online in STEM CELLSExpress December 18, 2008.

Abstract

The immunomodulatory activities of human mesenchymal stem cells (MSCs) provide a rational basis for their application in the treatment of immune-mediated diseases, such as graft versus host disease and multiple sclerosis. The effects of MSCs on invariant natural killer T (iNKT) and γδ T cells, both involved in the pathogenesis of autoimmune diseases, are unknown. Here, we investigated the effects of MSCs on in vitro expansion of these unconventional T-cell populations. MSCs inhibited iNKT (Vα24+Vβ11+) and γδ T (Vδ2+) cell expansion from peripheral blood mononuclear cells in both cell-to-cell contact and transwell systems. Such inhibition was partially counteracted by indomethacin, a prostaglandin E2 inhibitor. Block of indoleamine 2,3-deoxygenase and transforming growth factor β1 did not affect Vα24+Vβ11+ and Vδ2+ cell expansion. MSCs inhibited interferon-γ production by activated Vα24+Vβ11+ and impaired CD3-mediated proliferation of activated Vα24+Vβ11+ and Vδ2+ T cells, without affecting their cytotoxic potential. MSCs did not inhibit antigen processing/presentation by activated Vδ2+ T cells to CD4+ T cells. In contrast, MSCs were lysed by activated Vδ2+ T cells through a T-cell receptor-dependent mechanism. These results are translationally relevant in view of the increasing interest in MSC-based therapy of autoimmune diseases. STEM CELLS 2009;27:693–702

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