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A modified superantigen rescues Ly6G- CD11b+ blood monocyte suppressor function and suppresses antigen-specific inflammation in EAE

Slaney, Clare Y; Toker, Aras; Fraser, John D; Harper, Jacquie L and Bäckström, B Thomas LU (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
publishing date
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
  • 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
2019-02-20 11:30:05
@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},
  keyword      = {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},
  volume       = {46},
  year         = {2013},
}