Glatiramer acetate treatment directly targets CD11b(+)Ly6G(-) monocytes and enhances the suppression of autoreactive T cells in experimental autoimmune encephalomyelitis

Scand J Immunol. 2011 Sep;74(3):235-243. doi: 10.1111/j.1365-3083.2011.02575.x.


Glatiramer acetate (GA) is used for the treatment of relapsing-remitting multiple sclerosis (MS) and can suppress experimental autoimmune encephalomyelitis in animals. Effective GA treatment is associated with the induction of anti-inflammatory T(H)2 responses and antigen-specific expansion of CD25(+)/Foxp3(+) Tregs through the modulation of antigen-presenting cells. Here, we show that intravenous injection of fluorochrome-labelled GA resulted in rapid and specific binding of GA to CD11b(+) F4/80(lo) Ly6G(-) blood monocytes via an MHC class II-independent mechanism. Intravenous GA treatment enhanced the intrinsic capability of these monocytes to directly suppress T cell proliferation in vitro. The suppressive function correlated with reduced proliferation of myelin-specific T cells in vivo after intravenous GA treatment. In contrast, subcutaneous treatment with GA inhibited the pro-inflammatory IFNγ-producing T cell phenotype rather than suppressing T cell proliferation. These data indicate that (1) GA engages directly with circulating monocytes to induce type II monocyte suppressor function; and (2) the therapeutic efficacy of GA may be expanded by employing different routes of GA administration to engage alternative mechanisms of suppression of autoreactive T cells in MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / analysis
  • Autoimmunity
  • CD11b Antigen / analysis
  • Cell Proliferation
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Glatiramer Acetate
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myelin Sheath / immunology
  • Peptides / administration & dosage
  • Peptides / metabolism
  • Peptides / pharmacology*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology


  • Antigens, Ly
  • CD11b Antigen
  • Ly6G antigen, mouse
  • Peptides
  • Glatiramer Acetate
  • Interferon-gamma