Glatiramer acetate treatment directly targets CD11b(+)Ly6G(-) monocytes and enhances the suppression of autoreactive T cells in experimental autoimmune encephalomyelitis
(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.
(Less)
- author
- Toker, A ; Slaney, C Y ; Bäckström, B T LU and Harper, J L
- publishing date
- 2011-09
- 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
-
- pmid:21595733
- 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
- 2024-04-15 13:16:17
@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}},
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}},
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}},
doi = {{10.1111/j.1365-3083.2011.02575.x}},
volume = {{74}},
year = {{2011}},
}