Myeloid-derived suppressor cells regulate T cell and B cell responses during autoimmune disease

J Leukoc Biol. 2015 Mar;97(3):573-82. doi: 10.1189/jlb.4A0314-139R. Epub 2015 Jan 12.


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 naïve 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.

Keywords: autoimmune arthritis; chemokine receptor; collagen-induced arthritis; immunotherapy; rheumatoid arthritis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / therapy
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / therapy
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Dinoprostone / metabolism
  • Female
  • Immunization
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Monocytes / pathology
  • Myeloid Cells / immunology*
  • Myeloid Cells / transplantation
  • Nitric Oxide Synthase Type II / metabolism
  • Phenotype
  • Receptors, CCR2 / deficiency
  • Receptors, CCR2 / metabolism
  • T-Lymphocytes / immunology*


  • Ccr2 protein, mouse
  • Interleukin-17
  • Receptors, CCR2
  • Interferon-gamma
  • Nitric Oxide Synthase Type II
  • Dinoprostone