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    Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin

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    Author
    Suk, Lee, Y.
    Davila, E.
    Zhang, T.
    Date
    2019
    Journal
    Innate Immunity
    Publisher
    SAGE Publications Ltd
    Type
    Article
    
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    See at
    https://dx.doi.org/10.1177/1753425918820427
    Abstract
    Myeloid-derived suppressor cells (MDSCs) inhibit T cell responses and are relevant to cancer, autoimmunity and transplant biology. Anti-thymocyte globulin (ATG) is a commonly used T cell depletion agent, yet the effect of ATG on MDSCs has not been investigated. MDSCs were generated in Lewis Lung Carcinoma 1 tumor-bearing mice. MDSC development and function were assessed in vivo and in vitro with and without ATG administration. T cell suppression assays, RT-PCR, flow cytometry and arginase activity assays were used to assess MDSC phenotype and function. MDSCs increased dramatically in tumor-bearing mice and the majority of splenic MDSCs were of the polymorphonuclear subset. MDSCs potently suppressed T cell proliferation. ATG-treated mice developed 50% fewer MDSCs and these MDSCs were significantly less suppressive of T cell proliferation. In vitro, ATG directly bound 99.6% of MDSCs. CCR7, L-selectin and LFA-1 were expressed by both T cells and MDSCs, and binding of LFA-1 was inhibited by ATG pre-treatment. Arg-1 and PD-L1 transcript expression were reduced 30-40% and arginase activity decreased in ATG-pretreated MDSCs. MDSCs were bound and functionally inhibited by ATG. T cells and MDSCs expressed common Ags which were also targets of ATG. ATG may be helpful in tumor models seeking to suppress MDSCs. Alternatively, ATG may inadvertently inhibit important T cell regulatory events in autoimmunity and transplantation. © The Author(s) 2019.
    Keyword
    Antithymocyte globulin
    myeloid derived suppressor cells
    Transplant immunology
    transplantation tolerance
    Tregs
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85059661703&doi=10.1177%2f1753425918820427&partnerID=40&md5=94d80f3f463b1f9c1eea526ac5824447; http://hdl.handle.net/10713/8619
    ae974a485f413a2113503eed53cd6c53
    10.1177/1753425918820427
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