Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin
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 Car...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2019-01-01
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| Series: | Innate Immunity |
| Online Access: | https://doi.org/10.1177/1753425918820427 |
| _version_ | 1811294856501264384 |
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| author | Young Suk Lee Eduardo Davila Tianshu Zhang Hugh P Milmoe Stefanie N Vogel Jonathan S Bromberg Joseph R Scalea |
| author_facet | Young Suk Lee Eduardo Davila Tianshu Zhang Hugh P Milmoe Stefanie N Vogel Jonathan S Bromberg Joseph R Scalea |
| author_sort | Young Suk Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T05:23:47Z |
| format | Article |
| id | doaj.art-369ab15ddfeb4a71b5cc3d665313878c |
| institution | Directory Open Access Journal |
| issn | 1753-4259 1753-4267 |
| language | English |
| last_indexed | 2024-04-13T05:23:47Z |
| publishDate | 2019-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Innate Immunity |
| spelling | doaj.art-369ab15ddfeb4a71b5cc3d665313878c2022-12-22T03:00:39ZengSAGE PublishingInnate Immunity1753-42591753-42672019-01-012510.1177/1753425918820427Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulinYoung Suk LeeEduardo DavilaTianshu ZhangHugh P MilmoeStefanie N VogelJonathan S BrombergJoseph R ScaleaMyeloid-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.https://doi.org/10.1177/1753425918820427 |
| spellingShingle | Young Suk Lee Eduardo Davila Tianshu Zhang Hugh P Milmoe Stefanie N Vogel Jonathan S Bromberg Joseph R Scalea Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin Innate Immunity |
| title | Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin |
| title_full | Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin |
| title_fullStr | Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin |
| title_full_unstemmed | Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin |
| title_short | Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin |
| title_sort | myeloid derived suppressor cells are bound and inhibited by anti thymocyte globulin |
| url | https://doi.org/10.1177/1753425918820427 |
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