Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis
Top Cited Papers
- 18 November 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Biotechnology
- Vol. 30 (12), 1217-1224
- https://doi.org/10.1038/nbt.2434
Abstract
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.Keywords
This publication has 49 references indexed in Scilit:
- Antigen-Fixed Leukocytes Tolerize Th2 Responses in Mouse Models of AllergyPublished by The American Association of Immunologists ,2011
- MARCO Regulates Early Inflammatory Responses against InfluenzaAmerican Journal of Respiratory Cell and Molecular Biology, 2011
- A phase III study evaluating the efficacy and safety of MBP8298 in secondary progressive MSNeurology, 2011
- Tolerance Induced by Apoptotic Antigen-Coupled Leukocytes Is Induced by PD-L1+ and IL-10–Producing Splenic Macrophages and Maintained by T Regulatory CellsPublished by The American Association of Immunologists ,2011
- Glatiramer Acetate in the Treatment of Multiple SclerosisCNS Drugs, 2011
- Anti-class a scavenger receptor autoantibodies from systemic lupus erythematosus patients impair phagocytic clearance of apoptotic cells by macrophages in vitroArthritis Research & Therapy, 2011
- Scavenger receptors: role in innate immunity and microbial pathogenesisCellular Microbiology, 2009
- Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb teplizumab preserves insulin production for up to 5 yearsClinical Immunology, 2009
- PD‐1 ligands expressed on myeloid‐derived APC in the CNS regulate T‐cell responses in EAEEuropean Journal of Immunology, 2008
- Differential Binding of Inorganic Particles to MARCOToxicological Sciences, 2008