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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Getts, DR; Martin, AJ; McCarthy, DP; Terry, RL; Hunter, ZN; Yap, WT; Getts, MT; Pleiss, M; Luo, X; King, NJC; Shea, LD; Miller, SD

Published Date

  • December 2012

Published In

Volume / Issue

  • 30 / 12

Start / End Page

  • 1217 - 1224

PubMed ID

  • 23159881

Pubmed Central ID

  • 23159881

Electronic International Standard Serial Number (EISSN)

  • 1546-1696

International Standard Serial Number (ISSN)

  • 1087-0156

Digital Object Identifier (DOI)

  • 10.1038/nbt.2434

Language

  • eng