Protective DNA vaccination against myelin oligodendrocyte glycoprotein is overcome by C3d in experimental autoimmune encephalomyelitis.
Complement receptor 2 (CR2) and its physiological ligand, C3d, known for its molecular adjuvant property on the immune response, exhibit opposite effects with regard to autoimmunity. Although CR2 has been implicated in maintaining self-tolerance, recent studies reported a role for C3d signaling to CR2 in tolerance breakdown to self-antigens and the initiation of inflammatory autoimmune pathologies. In the present study, we have investigated the effect of C3d in a model of tolerogenic DNA vaccination encoding the myelin oligodendrocyte glycoprotein (MOG-DNA) which protected mice from the induction of an experimental autoimmune encephalomyelitis (EAE). We show that fusing two or three copies of C3d to MOG overcomes the protective effect of DNA vaccination. Multimeric C3d was able to revert the unresponsiveness state of specific T cells induced by MOG-DNA, independently of a modification in the Th1/Th2 cytokine pattern. Interestingly, the adjuvant effect of C3d was not sufficient to boost the anti-MOG antibody response after DNA vaccination. These findings suggest that C3d might be involved in self-tolerance breakdown and could contribute to the pathogenesis of central nervous system autoimmune disorders.
Jégou
Jean-François
JF
INSERM U413, IFRMP 23, Laboratory of Cellular and Molecular Neuroendocrinology, University of Rouen, 76821 Mont Saint-Aignan, France. jean-francous.jegou@univ-rouen.fr
Chan
Philippe
P
Schouft
Marie-Thérèse
MT
Gasque
Philippe
P
Vaudry
Hubert
H
Fontaine
Marc
M
D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D019556:COS Cells; D002522:Chlorocebus aethiops; D015933:Complement C3d / Q000276:immunology*; D004247:DNA / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D000276:Adjuvants, Immunologic; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D019444:Vaccines, DNA; D015933:Complement C3d; D004247:DNA