DEC-205-mediated antigen targeting to steady-state dendritic cells induces deletion of diabetogenic CD8⁺ T cells independently of PD-1 and PD-L1

Int Immunol. 2013 Nov;25(11):651-60. doi: 10.1093/intimm/dxt031. Epub 2013 Sep 10.


CD8⁺ T cells specific for islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) have been implicated in type 1 diabetes in both humans and non-obese diabetic (NOD) mice, in which T cells specific for IGRP₂₀₆₋₂₁₄ are highly prevalent. We sought to manipulate these pathogenic T cells by exploiting the ability of steady-state dendritic cells (DCs) to present antigens in a tolerogenic manner. The endocytic receptor DEC-205 was utilized to deliver an IGRP₂₀₆₋₂₁₄ mimotope to DCs in NOD mice, and the impact of this delivery on a polyclonal population of endogenous islet-reactive cognate T cells was determined. Assessment of islet-infiltrating CD8⁺ T cells showed a decrease in the percentage, and the absolute number, of endogenous IGRP₂₀₆₋₂₁₄-specific T cells when the mimotope was delivered to DCs, compared with delivery of a specificity control. Employing an adoptive transfer system, deletion of CD8⁺ T cells as a result of DEC-205-mediated antigen targeting was found to occur independently of programmed death-1 (PD-1) and its ligand (PD-L1), both often implicated in the regulation of peripheral T-cell tolerance. Given its promise for the manipulation of self-reactive polyclonal T cells demonstrated here, the distinctive characteristics of this antigen delivery system will be important to appreciate as its potential as an intervention for autoimmune diseases continues to be investigated.

Keywords: Autoimmunity; NOD mice; diabetes.

Publication types

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

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antigen-Antibody Reactions
  • Antigens / immunology*
  • Antigens, CD / immunology*
  • B7-H1 Antigen* / metabolism
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Lectins, C-Type / immunology*
  • Lymphocyte Count
  • Mice
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Minor Histocompatibility Antigens
  • Programmed Cell Death 1 Receptor* / metabolism
  • Receptors, Cell Surface / immunology*


  • Antibodies
  • Antigens
  • Antigens, CD
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • DEC-205 receptor
  • Lectins, C-Type
  • Minor Histocompatibility Antigens
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Receptors, Cell Surface