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

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

Nature biotechnology (2012-11-20)
Daniel R Getts, Aaron J Martin, Derrick P McCarthy, Rachael L Terry, Zoe N Hunter, Woon Teck Yap, Meghann Teague Getts, Michael Pleiss, Xunrong Luo, Nicholas J C King, Lonnie D Shea, Stephen D Miller
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Resomer® RG 505, Poly(D,L-lactide-co-glycolide), ester terminated, Mw 54,000-69,000
Sigma-Aldrich
Resomer® RG 504 H, Poly(D,L-lactide-co-glycolide), acid terminated, lactide:glycolide 50:50, Mw 38,000-54,000
Sigma-Aldrich
Resomer® RG 752 H, Poly(D,L-lactide-co-glycolide), acid terminated, lactide:glycolide 75:25, Mw 4,000-15,000
Sigma-Aldrich
Resomer® RG 502 H, Poly(D,L-lactide-co-glycolide), acid terminated, Mw 7,000-17,000
Sigma-Aldrich
Resomer® RG 653 H, Poly(D,L-lactide-co-glycolide), acid terminated, Mw 24,000-38,000
Sigma-Aldrich
Resomer® RG 503 H, Poly(D,L-lactide-co-glycolide), acid terminated, lactide:glycolide 50:50, Mw 24,000-38,000
Sigma-Aldrich
Resomer® RG 756 S, Poly(D,L-lactide-co-glycolide), ester terminated, lactide:glycolide 75:25, Mw 76,000-115,000
Sigma-Aldrich
Resomer® RG 502, Poly(D,L-Lactide-co-Glycolide), lactide:glycolide 50:50, ester terminated, Mw 7,000-17,000
Sigma-Aldrich
Poly(D,L-lactide-co-glycolide), lactide:glycolide 65:35, Mw 40,000-75,000
Sigma-Aldrich
Poly(D,L-lactide-co-glycolide), lactide:glycolide (75:25), mol wt 66,000-107,000
Sigma-Aldrich
Poly(D,L-lactide-co-glycolide), lactide:glycolide (50:50), mol wt 30,000-60,000
Sigma-Aldrich
Poly(D,L-lactide-co-glycolide), ester terminated, Mw 50,000-75,000
Sigma-Aldrich
Resomer® RG 858 S, Poly(D,L-lactide-co-glycolide), ester terminated, lactide:glycolide 85:15, Mw 190,000-240,000
Sigma-Aldrich
Resomer® RG 503, Poly(D,L-lactide-co-glycolide), lactide:glycolide 50:50, ester terminated, Mw 24,000-38,000
Sigma-Aldrich
Resomer® RG 504, Poly(D,L-lactide-co-glycolide), lactide:glycolide 50:50, ester terminated, Mw 38,000-54,000