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

Gayatri Mukherjee, Ari Geliebter, Jeffrey Babad, Pere Santamaria, David V. Serreze, Gordon J. Freeman, Kristin V. Tarbell, Arlene Sharpe, Teresa P. DiLorenzo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numberdxt031
Pages (from-to)651-660
Number of pages10
JournalInternational Immunology
Volume25
Issue number11
DOIs
StatePublished - Nov 2013

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Dendritic Cells
T-Lymphocytes
Antigens
Inbred NOD Mouse
Glucose-6-Phosphatase
Adoptive Transfer
Type 1 Diabetes Mellitus
Autoimmune Diseases
Catalytic Domain
Ligands
Population

Keywords

  • Autoimmunity
  • Diabetes
  • NOD mice

ASJC Scopus subject areas

  • Immunology

Cite this

DEC-205-mediated antigen targeting to steady-state dendritic cells induces deletion of diabetogenic CD8+ T cells independently of PD-1 and PD-L1. / Mukherjee, Gayatri; Geliebter, Ari; Babad, Jeffrey; Santamaria, Pere; Serreze, David V.; Freeman, Gordon J.; Tarbell, Kristin V.; Sharpe, Arlene; DiLorenzo, Teresa P.

In: International Immunology, Vol. 25, No. 11, dxt031, 11.2013, p. 651-660.

Research output: Contribution to journalArticle

Mukherjee, G, Geliebter, A, Babad, J, Santamaria, P, Serreze, DV, Freeman, GJ, Tarbell, KV, Sharpe, A & DiLorenzo, TP 2013, 'DEC-205-mediated antigen targeting to steady-state dendritic cells induces deletion of diabetogenic CD8+ T cells independently of PD-1 and PD-L1', International Immunology, vol. 25, no. 11, dxt031, pp. 651-660. https://doi.org/10.1093/intimm/dxt031
Mukherjee, Gayatri ; Geliebter, Ari ; Babad, Jeffrey ; Santamaria, Pere ; Serreze, David V. ; Freeman, Gordon J. ; Tarbell, Kristin V. ; Sharpe, Arlene ; DiLorenzo, Teresa P. / DEC-205-mediated antigen targeting to steady-state dendritic cells induces deletion of diabetogenic CD8+ T cells independently of PD-1 and PD-L1. In: International Immunology. 2013 ; Vol. 25, No. 11. pp. 651-660.
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