title: Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis.
abstract: Aberrant T-cell activation underlies many autoimmune disorders, yet most attempts to induce T-cell tolerance have failed. Building on previous strategies for tolerance induction that exploited natural mechanisms for clearing apoptotic debris, we show that antigen-decorated microparticles (500-nm diameter) induce long-term T-cell tolerance in mice with relapsing experimental autoimmune encephalomyelitis. Specifically, intravenous infusion of either polystyrene or biodegradable poly(lactide-co-glycolide) microparticles bearing encephalitogenic peptides prevents the onset and modifies the course of the disease. These beneficial effects require microparticle uptake by marginal zone macrophages expressing the scavenger receptor MARCO and are mediated in part by the activity of regulatory T cells, abortive T-cell activation and T-cell anergy. Together these data highlight the potential for using microparticles to target natural apoptotic clearance pathways to inactivate pathogenic T cells and halt the disease process in autoimmunity.
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Getts
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Martin
authors.forename: Derrick P
authors.initials: DP
authors.lastname: McCarthy
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Terry
authors.forename: Zoe N
authors.initials: ZN
authors.lastname: Hunter
authors.forename: Woon Teck
authors.initials: WT
authors.lastname: Yap
authors.forename: Meghann Teague
authors.initials: MT
authors.lastname: Getts
authors.forename: Michael
authors.initials: M
authors.lastname: Pleiss
authors.forename: Xunrong
authors.initials: X
authors.lastname: Luo
authors.forename: Nicholas J C
authors.initials: NJ
authors.lastname: King
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Miller
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage; D001709:Biotechnology; D017635:Clonal Anergy; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D007108:Immune Tolerance; D007262:Infusions, Intravenous; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008863:Microspheres; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage* / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D011098:Polyglactin 910; D011137:Polystyrenes; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D001324:Autoantigens; C556062:IL10 protein, mouse; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011137:Polystyrenes; C435023:myelin proteolipid protein (139-151); D016753:Interleukin-10; C094242:myelin proteolipid protein (178-191); D011098:Polyglactin 910