Premium
Glatiramer Acetate Treatment Directly Targets CD11b + Ly6G − Monocytes and Enhances the Suppression of Autoreactive T cells in Experimental Autoimmune Encephalomyelitis
Author(s) -
Toker A.,
Slaney C. Y.,
Bäckström B. T.,
Harper J. L.
Publication year - 2011
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2011.02575.x
Subject(s) - glatiramer acetate , experimental autoimmune encephalomyelitis , immunology , multiple sclerosis , il 2 receptor , foxp3 , antigen , t cell , monocyte , encephalomyelitis , medicine , mhc class ii , chemistry , immune system
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.