Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis

• Published in: Nature biotechnology Vol. 30; no. 12; pp. 1217 - 1224
• Main Authors: Getts, Daniel R, Martin, Aaron J, McCarthy, Derrick P, Terry, Rachael L, Hunter, Zoe N, Yap, Woon Teck, Getts, Meghann Teague, Pleiss, Michael, Luo, Xunrong, King, Nicholas JC, Shea, Lonnie D, Miller, Stephen D
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-12-2012; Nature Publishing Group
• Subjects: 631/250/2152/569; 631/61/54; 692/699/249/1313; Agriculture; Anergy; Animals; Antigens; Apoptosis; Autoantigens - administration & dosage; Autoimmune diseases; Biodegradation; Bioinformatics; Biological and medical sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Clonal Anergy; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - prevention & control; Female; Fundamental and applied biological sciences. Psychology; Immune system; Immune Tolerance; Infusions, Intravenous; Interleukin-10 - immunology; Life Sciences; Lymphocyte Activation; Lymphocytes; Mice; Microspheres; Myelin Proteolipid Protein - administration & dosage; Myelin Proteolipid Protein - immunology; Peptide Fragments - administration & dosage; Peptide Fragments - immunology; Peptides; Physiological aspects; Polyglactin 910; Polystyrenes; T cells; T-Lymphocytes - immunology; T-Lymphocytes, Regulatory - immunology; Autoimmunity; Multiple sclerosis; Encephalomyelitis; Peptides; Tolerance; Autoimmune disease; Microparticle
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.2434

Microparticles coated with encephalitogenic peptides are effective at treating multiple sclerosis in a mouse model.
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.