期刊
DIABETES
卷 66, 期 8, 页码 2220-2229出版社
AMER DIABETES ASSOC
DOI: 10.2337/db16-0946
关键词
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资金
- National Institute of Diabetes and Digestive and Kidney Diseases grant [P30-DK-036836]
- Mary K. Iacocca Fellowship by the Iacocca Foundation
- Swedish Society of Medicine
- Tegger Foundation
- Swedish Society for Medical Research
- Fleisher Family Foundation
- Pittsburgh Foundation
- Harvard Stem Cell Institute
Dysfunctional T cells can mediate autoimmunity, but the inaccessibility of autoimmune tissues and the rarity of autoimmune T cells in the blood hinder their study. We describe a method to enrich and harvest autoimmune T cells in vivo by using a biomaterial scaffold loaded with protein antigens. In model antigen systems, we found that antigen-specific T cells become enriched within scaffolds containing their cognate antigens. When scaffolds containing lysates from an insulin-producing -cell line were implanted subcutaneously in autoimmune diabetes-prone NOD mice, -cell-reactive T cells homed to these scaffolds and became enriched. These T cells induced diabetes after adoptive transfer, indicating their pathogenicity. Furthermore, T-cell receptor (TCR) sequencing identified many expanded TCRs within the -cell scaffolds that were also expanded within the pancreata of NOD mice. These data demonstrate the utility of biomaterial scaffolds loaded with disease-specific antigens to identify and study rare, therapeutically important T cells.
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