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

Nat Biotechnol. 2012 Dec;30(12):1217-24. doi: 10.1038/nbt.2434. Epub 2012 Nov 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / administration & dosage
  • Biotechnology
  • Clonal Anergy
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Female
  • Immune Tolerance*
  • Infusions, Intravenous
  • Interleukin-10 / immunology
  • Lymphocyte Activation
  • Mice
  • Microspheres
  • Myelin Proteolipid Protein / administration & dosage*
  • Myelin Proteolipid Protein / immunology*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Polyglactin 910
  • Polystyrenes
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology


  • Autoantigens
  • IL10 protein, mouse
  • Myelin Proteolipid Protein
  • Peptide Fragments
  • Polystyrenes
  • myelin proteolipid protein (139-151)
  • Interleukin-10
  • myelin proteolipid protein (178-191)
  • Polyglactin 910