In Vivo Enrichment of Diabetogenic T Cells.

ABSTRACT: 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.

SUBMITTER: Thelin MA 

PROVIDER: S-EPMC5521861 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature