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    Multipotent Adult Progenitor Cells Suppress T Cell Activation in In Vivo Models of Homeostatic Proliferation in a Prostaglandin E2-Dependent Manner


    Carty, Fiona and Corbett, Jennifer and Cunha, João Paulo M. C. M. and Reading, James and Tree, Timothy and Ting, Anthony E. and Stubblefield, Samatha R. and English, Karen (2018) Multipotent Adult Progenitor Cells Suppress T Cell Activation in In Vivo Models of Homeostatic Proliferation in a Prostaglandin E2-Dependent Manner. Frontiers in Immunology, 6 (645). ISSN 1664-3224

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    Abstract

    Lymphodepletion strategies are used in the setting of transplantation (including bone marrow, hematopoietic cell, and solid organ) to create space or to prevent allograft rejection and graft versus host disease. Following lymphodepletion, there is an excess of IL-7 available, and T cells that escape depletion respond to this cytokine undergoing accelerated proliferation. Moreover, this environment promotes the skew of T cells to a Th1 pro-inflammatory phenotype. Existing immunosuppressive regimens fail to control this homeostatic proliferative (HP) response, and thus the development of strategies to successfully control HP while sparing T cell reconstitution (providing a functioning immune system) represents a significant unmet need in patients requiring lymphodepletion. Multipotent adult progenitor cells (MAPC®) have the capacity to control T cell proliferation and Th1 cytokine production. Herein, this study shows that MAPC cells suppressed anti-thymocyte globulin-induced cytokine production but spared T cell reconstitution in a pre-clinical model of lymphodepletion. Importantly, MAPC cells administered intraperitoneally were efficacious in suppressing interferon-γ production and in promoting the expansion of regulatory T cells in the lymph nodes. MAPC cells administered intraperitoneally accumulated in the omentum but were not present in the spleen suggesting a role for soluble factors. MAPC cells suppressed lymphopenia-induced cytokine production in a prostaglandin E2-dependent manner. This study suggests that MAPC cell therapy may be useful as a novel strategy to target lymphopenia-induced pathogenic T cell responses in lymphodepleted patients.

    Item Type: Article
    Keywords: multipotent adult progenitor cells; mesenchymal stromal cells; homeostatic proliferation; IL-7; antithymocyte globulin; prostaglandin E2;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 10576
    Identification Number: https://doi.org/10.3389/fimmu.2018.00645
    Depositing User: Karen English
    Date Deposited: 25 Feb 2019 10:52
    Journal or Publication Title: Frontiers in Immunology
    Publisher: Frontiers Media
    Refereed: Yes
    URI:

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