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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
External organisations
  • Malaghan Institute of Medical Research
  • Novo Nordisk A/S
Research areas and keywords

Keywords

  • Animals, Antigens, Ly/analysis, Autoimmunity, CD11b Antigen/analysis, Cell Proliferation, Encephalomyelitis, Autoimmune, Experimental/drug therapy, Glatiramer Acetate, Interferon-gamma/metabolism, Leukocytes, Mononuclear/drug effects, Lymphocyte Activation/drug effects, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myelin Sheath/immunology, Peptides/administration & dosage, T-Lymphocyte Subsets/drug effects, Th2 Cells/drug effects
Original languageEnglish
Pages (from-to)235-243
JournalScandinavian Journal of Immunology
Volume74
Issue number3
Publication statusPublished - 2011 Sep
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes