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

Toker, A; Slaney, C Y; Bäckström, B T LU and Harper, J L (2011) In Scandinavian Journal of Immunology 74(3). p.235-243
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... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
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
in
Scandinavian Journal of Immunology
volume
74
issue
3
pages
235 - 243
publisher
Wiley-Blackwell
external identifiers
  • scopus:79961122749
ISSN
1365-3083
DOI
10.1111/j.1365-3083.2011.02575.x
language
English
LU publication?
no
id
41571a23-d407-4a76-9591-c4cd2f445c47
date added to LUP
2018-10-08 22:12:23
date last changed
2019-09-11 04:04:28
@article{41571a23-d407-4a76-9591-c4cd2f445c47,
  abstract     = {<p>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.</p>},
  author       = {Toker, A and Slaney, C Y and Bäckström, B T and Harper, J L},
  issn         = {1365-3083},
  keyword      = {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},
  language     = {eng},
  number       = {3},
  pages        = {235--243},
  publisher    = {Wiley-Blackwell},
  series       = {Scandinavian Journal of Immunology},
  title        = {Glatiramer acetate treatment directly targets CD11b(+)Ly6G(-) monocytes and enhances the suppression of autoreactive T cells in experimental autoimmune encephalomyelitis},
  url          = {http://dx.doi.org/10.1111/j.1365-3083.2011.02575.x},
  volume       = {74},
  year         = {2011},
}