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

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

Author information

1
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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.

KEYWORDS:

Autoimmunity; NOD mice; diabetes

PMID:
24021877
PMCID:
PMC3806169
DOI:
10.1093/intimm/dxt031
[Indexed for MEDLINE]
Free PMC Article

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