title: Active suppression induced by repetitive self-epitopes protects against EAE development.
abstract: BACKGROUND
  Autoimmune diseases result from a breakdown in self-tolerance to autoantigens. Self-tolerance is induced and sustained by central and peripheral mechanisms intended to deviate harmful immune responses and to maintain homeostasis, where regulatory T cells play a crucial role. The use of self-antigens in the study and treatment of a range of autoimmune diseases has been widely described; however, the mechanisms underlying the induced protection by these means are unclear. This study shows that protection of experimental autoimmune disease induced by T cell self-epitopes in a multimerized form (oligomers) is mediated by the induction of active suppression.
  
  
  RESULTS
  The experimental autoimmune encephalomyelitis (EAE) animal model for multiple sclerosis was used to study the mechanisms of protection induced by the treatment of oligomerized T cell epitope of myelin proteolipid protein (PLP139-151). Disease protection attained by the administration of oligomers was shown to be antigen specific and effective in both prevention and treatment of ongoing EAE. Oligomer mediated tolerance was actively transferred by cells from treated mice into adoptive hosts. The induction of active suppression was correlated with the recruitment of cells in the periphery associated with increased production of IL-10 and reduction of the pro-inflammatory cytokine TNF-α. The role of suppressive cytokines was demonstrated by the reversion of oligomer-induced protection after in vivo blocking of either IL-10 or TGF-β cytokines.
  
  
  CONCLUSIONS
  This study strongly supports an immunosuppressive role of repeat auto-antigens to control the development of EAE with potential applications in vaccination and antigen specific treatment of autoimmune diseases.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany. f.puentes@qmul.ac.uk
authors.forename: Fabiola
authors.initials: F
authors.lastname: Puentes
authors.forename: Katharina
authors.initials: K
authors.lastname: Dickhaut
authors.forename: Maria
authors.initials: M
authors.lastname: Hofstätter
authors.forename: Kirsten
authors.initials: K
authors.lastname: Falk
authors.forename: Olaf
authors.initials: O
authors.lastname: Rötzschke
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control* / Q000628:therapy; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D007165:Immunosuppression Therapy / Q000379:methods*; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D001324:Autoantigens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments