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.
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Authors | Gayatri Mukherjee, Ari Geliebter, Jeffrey Babad, Pere Santamaria, David V Serreze, Gordon J Freeman, Kristin V Tarbell, Arlene Sharpe, Teresa P DiLorenzo |
Journal | International immunology
(Int Immunol)
Vol. 25
Issue 11
Pg. 651-60
(Nov 2013)
ISSN: 1460-2377 [Electronic] England |
PMID | 24021877
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- 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
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Topics |
- Animals
- Antibodies
(immunology)
- Antigen-Antibody Reactions
- Antigens
(immunology)
- Antigens, CD
(immunology)
- B7-H1 Antigen
(metabolism)
- CD8-Positive T-Lymphocytes
(cytology, immunology)
- Dendritic Cells
(cytology, 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)
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