A modified superantigen rescues Ly6G- CD11b+ blood monocyte suppressor function and suppresses antigen-specific inflammation in EAE
(2013) In Autoimmunity 46(4). p.78-269- Abstract
In a previous study, we showed that the Ly6G(-)CD11b(+) blood monocytes residing in naïve mice are intrinsically immunosuppressive and that loss of this suppressive function may contribute to the development of autoimmunity in experimental autoimmune encephalomyelitis (EAE), a murine model of human multiple sclerosis. Here we report that mice treated with a modified superantigen coupled to myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) peptide (DM-MOG(35-55)) suppressed the development of EAE. The treatment was associated with impaired MOG(35-55)-specific T cell proliferation and a decrease in IL-17 and IFNγ production in the draining lymph nodes. Analysis of circulating blood immune cells showed that the suppressor function of... (More)
In a previous study, we showed that the Ly6G(-)CD11b(+) blood monocytes residing in naïve mice are intrinsically immunosuppressive and that loss of this suppressive function may contribute to the development of autoimmunity in experimental autoimmune encephalomyelitis (EAE), a murine model of human multiple sclerosis. Here we report that mice treated with a modified superantigen coupled to myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) peptide (DM-MOG(35-55)) suppressed the development of EAE. The treatment was associated with impaired MOG(35-55)-specific T cell proliferation and a decrease in IL-17 and IFNγ production in the draining lymph nodes. Analysis of circulating blood immune cells showed that the suppressor function of Ly6G(-)CD11b(+) blood monocytes was reduced in EAE mice, but was restored in mice treated with DM-MOG(35-55). Importantly, adoptive transfer of blood CD11b(+)Ly6G(-) cells isolated from DM-MOG(35-55)-treated mice protected recipient mice from developing EAE. Together, these results show that DM coupled to the auto-antigen MOG(35-55): 1) suppresses EAE via antigen-specific suppression of T cell responses, and 2) re-establishes suppressor function of Ly6G(-)CD11b(+) blood monocytes. Auto-antigens coupled to DM could therefore represent a new therapeutic approach for controlling inappropriate inflammation in autoimmune diseases such as multiple sclerosis by inducing antigen-specific T cell suppression.
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- author
- Slaney, Clare Y ; Toker, Aras ; Fraser, John D ; Harper, Jacquie L and Bäckström, B Thomas LU
- publishing date
- 2013-06
- type
- Contribution to journal
- publication status
- published
- keywords
- Adoptive Transfer, Animals, Antigens, Ly/metabolism, Bacterial Toxins/chemistry, CD11b Antigen/metabolism, Encephalomyelitis, Autoimmune, Experimental/immunology, Epitopes/immunology, Exotoxins/chemistry, Lymphocyte Activation/immunology, Mice, Monocytes/immunology, Myelin-Oligodendrocyte Glycoprotein/chemistry, Peptide Fragments/chemistry, Superantigens/immunology, T-Lymphocyte Subsets/immunology
- in
- Autoimmunity
- volume
- 46
- issue
- 4
- pages
- 78 - 269
- publisher
- Taylor & Francis
- external identifiers
-
- pmid:23374140
- scopus:84877778047
- ISSN
- 0891-6934
- DOI
- 10.3109/08916934.2013.767893
- language
- English
- LU publication?
- no
- id
- 9045fc0b-d849-45e7-87b0-d442342458bc
- date added to LUP
- 2018-10-08 22:10:59
- date last changed
- 2024-01-15 03:16:39
@article{9045fc0b-d849-45e7-87b0-d442342458bc,
abstract = {{<p>In a previous study, we showed that the Ly6G(-)CD11b(+) blood monocytes residing in naïve mice are intrinsically immunosuppressive and that loss of this suppressive function may contribute to the development of autoimmunity in experimental autoimmune encephalomyelitis (EAE), a murine model of human multiple sclerosis. Here we report that mice treated with a modified superantigen coupled to myelin oligodendrocyte glycoprotein 35-55 (MOG(35-55)) peptide (DM-MOG(35-55)) suppressed the development of EAE. The treatment was associated with impaired MOG(35-55)-specific T cell proliferation and a decrease in IL-17 and IFNγ production in the draining lymph nodes. Analysis of circulating blood immune cells showed that the suppressor function of Ly6G(-)CD11b(+) blood monocytes was reduced in EAE mice, but was restored in mice treated with DM-MOG(35-55). Importantly, adoptive transfer of blood CD11b(+)Ly6G(-) cells isolated from DM-MOG(35-55)-treated mice protected recipient mice from developing EAE. Together, these results show that DM coupled to the auto-antigen MOG(35-55): 1) suppresses EAE via antigen-specific suppression of T cell responses, and 2) re-establishes suppressor function of Ly6G(-)CD11b(+) blood monocytes. Auto-antigens coupled to DM could therefore represent a new therapeutic approach for controlling inappropriate inflammation in autoimmune diseases such as multiple sclerosis by inducing antigen-specific T cell suppression.</p>}},
author = {{Slaney, Clare Y and Toker, Aras and Fraser, John D and Harper, Jacquie L and Bäckström, B Thomas}},
issn = {{0891-6934}},
keywords = {{Adoptive Transfer; Animals; Antigens, Ly/metabolism; Bacterial Toxins/chemistry; CD11b Antigen/metabolism; Encephalomyelitis, Autoimmune, Experimental/immunology; Epitopes/immunology; Exotoxins/chemistry; Lymphocyte Activation/immunology; Mice; Monocytes/immunology; Myelin-Oligodendrocyte Glycoprotein/chemistry; Peptide Fragments/chemistry; Superantigens/immunology; T-Lymphocyte Subsets/immunology}},
language = {{eng}},
number = {{4}},
pages = {{78--269}},
publisher = {{Taylor & Francis}},
series = {{Autoimmunity}},
title = {{A modified superantigen rescues Ly6G- CD11b+ blood monocyte suppressor function and suppresses antigen-specific inflammation in EAE}},
url = {{http://dx.doi.org/10.3109/08916934.2013.767893}},
doi = {{10.3109/08916934.2013.767893}},
volume = {{46}},
year = {{2013}},
}