CD11b+Ly-6C(hi) suppressive monocytes in experimental autoimmune encephalomyelitis

J Immunol. 2007 Oct 15;179(8):5228-37. doi: 10.4049/jimmunol.179.8.5228.

Abstract

Innate immune cells may regulate adaptive immunity by balancing different lineages of T cells and providing negative costimulation. In addition, CD11b(+)Gr-1(+) myeloid-derived suppressor cells have been described in tumor, parasite infection, and severe trauma models. In this study, we observe that splenic CD11b(+) cells markedly increase after experimental autoimmune encephalomyelitis (EAE) immunization, and they suppress T cell proliferation in vitro. Although >80% of CD11b(+) cells express varying levels of Gr-1, only a small population of CD11b(+)Ly-6C(high) inflammatory monocytes (IMC) can efficiently suppress T cell proliferation and induce T cell apoptosis through the production of NO. IFN-gamma produced by activated T cells is essential to induce IMC suppressive function. EAE immunization increases the frequencies of IMC in the bone marrow, spleen, and blood, but not in the lymph nodes. At the peak of EAE, IMC represent approximately 30% of inflammatory cells in the CNS. IMC express F4/80 and CD93 but not CD31, suggesting that they are immature monocytes. Furthermore, IMC have the plasticity to up-regulate NO synthase 2 or arginase 1 expression upon different cytokine treatments. These findings indicate that CD11b(+)Ly-6C(high) IMC induced during EAE priming are powerful suppressors of activated T cells. Further understanding of suppressive monocytes in autoimmune disease models may have important clinical implications for human autoimmune diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Ly / biosynthesis*
  • Antigens, Ly / metabolism
  • Antigens, Ly / physiology
  • Apoptosis / immunology
  • CD11b Antigen / biosynthesis*
  • CD11b Antigen / physiology
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Immunophenotyping
  • Immunosuppression Therapy
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Monocytes / immunology*
  • Monocytes / metabolism*
  • Monocytes / pathology
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology

Substances

  • Antigens, Ly
  • CD11b Antigen
  • Ly-6C antigen, mouse
  • Ly6G antigen, mouse