| First Author | Mukherjee G | Year | 2013 |
| Journal | Int Immunol | Volume | 25 |
| Issue | 11 | Pages | 651-60 |
| PubMed ID | 24021877 | Mgi Jnum | J:202027 |
| Mgi Id | MGI:5516518 | Doi | 10.1093/intimm/dxt031 |
| Citation | Mukherjee G, et al. (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. Int Immunol 25(11):651-60 |
| abstractText | 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. |
