title: A modified superantigen rescues Ly6G- CD11b+ blood monocyte suppressor function and suppresses antigen-specific inflammation in EAE.
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 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.
authors: Malaghan Institute of Medical Research, Wellington, New Zealand.
authors: Clare Y
authors: CY
authors: Slaney
authors: Aras
authors: A
authors: Toker
authors: John D
authors: JD
authors: Fraser
authors: Jacquie L
authors: JL
authors: Harper
authors: B Thomas
authors: BT
authors: Bäckström
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry / Q000276:immunology; D039481:CD11b Antigen / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D000939:Epitopes / Q000276:immunology*; D005098:Exotoxins / Q000737:chemistry / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D001427:Bacterial Toxins; D039481:CD11b Antigen; D000939:Epitopes; D005098:Exotoxins; C480309:Ly6G antigen, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D018089:Superantigens; C107894:mitogenic exotoxin Z protein, Streptococcus; C445081:myelin oligodendrocyte glycoprotein (35-55)