Myeloid-derived suppressor cells regulate T cell and B cell responses during autoimmune disease
Autor: | Denise Esserman, Mengyao Jin, Rishi R. Rampersad, Peng Liu, Todd A. Schwartz, Michael F. Weeks, Robert M. Baldi, Yajuan Shen, Kristen R. Crook, Amy S. Glekas, Paul Little |
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Rok vydání: | 2015 |
Předmět: |
CD4-Positive T-Lymphocytes
Male Adoptive cell transfer CCR2 Receptors CCR2 animal diseases T-Lymphocytes medicine.medical_treatment T cell Immunology Nitric Oxide Synthase Type II Biology Dinoprostone Monocytes Autoimmune Diseases Interferon-gamma Chemokine receptor parasitic diseases medicine Animals Immunology and Allergy Myeloid Cells B cell Cell Proliferation Autoimmune disease B-Lymphocytes Interleukin-17 Cell Biology Immunotherapy Host Defense & Pathophysiology medicine.disease Arthritis Experimental Mice Inbred C57BL Phenotype medicine.anatomical_structure Mice Inbred DBA Antibody Formation Myeloid-derived Suppressor Cell Female Immunization |
Zdroj: | Journal of Leukocyte Biology. 97:573-582 |
ISSN: | 1938-3673 0741-5400 |
DOI: | 10.1189/jlb.4a0314-139r |
Popis: | MDSCs are a heterogeneous group of myeloid cells that suppress T cell activity in cancer and autoimmune disease. The effect of MDSCs on B cell function is not clear. Using the CIA model of autoimmune disease, we found an increase in M-MDSCs in the periphery of WT mice with CIA compared with nai¨ve mice. These MDSCs were absent from the periphery of CCR2−/− mice that developed exacerbated disease. M-MDSCs, isolated from immunized mice, inhibited autologous CD4+ T cell proliferation. The M-MDSC-mediated suppression of T cell proliferation was NO and IFN-γ dependent but IL-17 independent. Furthermore, we demonstrated for the first time that M-MDSCs from CIA mice also inhibited autologous B cell proliferation and antibody production. The suppression of B cells by M-MDSCs was dependent on the production of NO and PGE2 and required cell–cell contact. Administration of M-MDSCs rescued CCR2−/− mice from the exacerbated CIA phenotype and ameliorated disease in WT mice. Furthermore, adoptive transfer of M-MDSCs reduced autoantibody production by CCR2−/− and WT mice. In summary, M-MDSCs inhibit T cell and B cell function in CIA and may serve as a therapeutic approach in the treatment of autoimmune arthritis. |
Databáze: | OpenAIRE |
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