In Vivo Enrichment of Diabetogenic T Cells

Diabetes. 2017 Aug;66(8):2220-2229. doi: 10.2337/db16-0946. Epub 2017 Apr 10.

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 β-cell line were implanted subcutaneously in autoimmune diabetes-prone NOD mice, β-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 β-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods
  • Animals
  • Antigens / administration & dosage
  • Autoimmunity / immunology
  • Cell Line
  • Cell Movement
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Insulin-Secreting Cells / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Pancreas / immunology
  • Receptors, Antigen, T-Cell / analysis
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Tissue Scaffolds / chemistry

Substances

  • Antigens
  • Receptors, Antigen, T-Cell