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

作者：Mukherjee Gayatri; Geliebter Ari; Babad Jeffrey; Santamaria Pere; Serreze David V; Freeman Gordon J; Tarbell Kristin V; Sharpe Arlene; DiLorenzo Teresa P^*

来源：International Immunology, 2013, 25(11): 651-660.

DOI：10.1093/intimm/dxt031

• Autoimmunity
• diabetes
• NOD mice

Targeting antigen to steady state DCs causes deletion of endogenous islet-specific T cells.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 IGRP(206214) 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 IGRP(206214) 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 IGRP(206214)-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.

• 出版日期2013-11