title: Glatiramer acetate treatment directly targets CD11b(+)Ly6G(-) monocytes and enhances the suppression of autoreactive T cells in experimental autoimmune encephalomyelitis.
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.
authors: Malaghan Institute of Medical Research, Wellington, New ZealandDepartment of T Cell Biology, Biopharmaceuticals Research Unit, Novo Nordisk A/S, Måløv, Denmark.
authors: A
authors: A
authors: Toker
authors: Malaghan Institute of Medical Research, Wellington, New ZealandDepartment of T Cell Biology, Biopharmaceuticals Research Unit, Novo Nordisk A/S, Måløv, Denmark.
authors: C Y
authors: CY
authors: Slaney
authors: Malaghan Institute of Medical Research, Wellington, New ZealandDepartment of T Cell Biology, Biopharmaceuticals Research Unit, Novo Nordisk A/S, Måløv, Denmark.
authors: B T
authors: BT
authors: Bäckström
authors: Malaghan Institute of Medical Research, Wellington, New ZealandDepartment of T Cell Biology, Biopharmaceuticals Research Unit, Novo Nordisk A/S, Måløv, Denmark.
authors: J L
authors: JL
authors: Harper