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Down-Regulation under Chronic Inflammation Is Mediated by Myeloid Suppressor Cells Differentially Distributed between Various Lymphatic Organs1
* The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel;
Department of Periodontology, The Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem, Israel; and
Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
T cell AgR 
chain down-regulation associated with T cell dysfunction has been described in cancer, infectious, and autoimmune diseases. We have previously shown that chronic inflammation is mandatory for the induction of an immunosuppressive environment leading to this phenomenon. To identify the key immunosuppressive components, we used an in vivo mouse model exhibiting chronic inflammation-induced immunosuppression. Herein, we demonstrate that: 1) under chronic inflammation secondary lymphatic organs display various immunological milieus; chain down-regulation and T cell dysfunction are induced in the spleen, peripheral blood, and bone marrow, but not in lymph nodes, correlating with elevated levels of Gr1+Mac-1+ myeloid suppressor cells (MSC); 2) MSC are responsible for the induction of such an immunosuppression under both normal and inflammatory conditions; and 3) normal T cells administered into mice exhibiting an immunosuppressive environment down-regulate their expression. Such an environment is anticipated to limit the success of immunotherapeutic strategies based on vaccination and T cell transfer, which are currently under investigation for immunotherapy of cancer.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported by the Israel Academy of Sciences and Humanities, by the Israeli Ministry of Health, by the Israel Cancer Association, by the Joint German-Israeli Research Program (Deutsches Krebsforschungszentrum), Israel Cancer Research Fund, and by the Herman Elbin and The Joseph and Matilda Melnick funds.
2 Address correspondence and reprint requests to Dr. Michal Baniyash, The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem 91120, Israel. E-mail address: baniyash{at}cc.huji.ac.il
3 Abbreviation used in this paper: MSC, myeloid suppressor cell.
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