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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. [ABSTRACT FROM AUTHOR]

A correction to the article "Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis" that was published in the June 4, 2013 issue is presented.

Abstract: A vaccine targeting the amyloid-beta (Aβ) peptide is a promising potential immunotherapy for Alzheimer''s disease patients. However, experience from a recent clinical trial of a candidate Aβ vaccine has suggested that it is important to develop techniques to induce high titer antibodies against Aβ associated with vaccine efficacy while reducing the T cell responses against Aβ that were potentially responsible for serious side effects. We have previously demonstrated that immunization with self- and foreign antigens arrayed in a repetitive fashion on the surface of virus-like particles (VLPs) induces high titer antibody responses at low doses and in the absence of potentially inflammatory adjuvants. In this study, we examined the antibody and T cell responses upon immunization with human papillomavirus VLP- and Qβ bacteriophage-based Aβ vaccines. Immunization with Aβ conjugated to VLPs or Qβ elicited anti-Aβ antibody responses at low doses and without the use of adjuvants. The flexibility of these virus-based display systems allowed us to link and induce antibodies against short Aβ-derived peptides from the amino- and carboxyl-termini of the peptide. Immunization of mice with Aβ peptide in combination with Freund''s adjuvant elicited predominantly IgG2c antibodies and strong T cell proliferative responses against Aβ. In contrast, VLP-conjugated Aβ peptides elicited more balanced isotype responses, dominated by IgG1. Both VLP and Qβ-based Aβ vaccines induced weak or negligible T cell responses against Aβ. T cell responses were largely directed against linked viral epitopes. Taken together, virus-based vaccines that allow the presentation of Aβ in a repetitive dense array are new and potentially more effective vaccine candidates for Alzheimer''s disease. [Copyright &y& Elsevier]