Tolerance induction by liposomes targeting a single CD8 epitope IGRP206-214 in a model of type 1 diabetes is impeded by co-targeting a CD4+ islet epitope.
Immunol Cell Biol
; 100(1): 33-48, 2022 01.
Article
en En
| MEDLINE
| ID: mdl-34668580
ABSTRACT
The autoimmune disease type 1 diabetes is predominantly mediated by CD8+ cytotoxic T-cell destruction of islet beta cells, of which islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)206-214 is a dominant target antigen specificity. Previously, we found that a liposome-based antigen-specific immunotherapy encapsulating the CD4+ T-cell islet epitope 2.5mim together with the nuclear factor-κB inhibitor calcitriol induced regulatory T cells and protected from diabetes in NOD mice. Here we investigated whether the same system delivering IGRP206-214 could induce antigen-specific CD8+ T-cell-targeted immune regulation and delay diabetes. Subcutaneous administration of IGRP206-214 /calcitriol liposomes transiently activated and expanded IGRP-specific T-cell receptor transgenic 8.3 CD8+ T cells. Liposomal co-delivery of calcitriol was required to optimally suppress endogenous IGRP-specific CD8+ T-cell interferon-γ production and cytotoxicity. Concordantly, a short course of IGRP206-214 /calcitriol liposomes delayed diabetes progression and reduced insulitis. However, when IGRP206-214 /calcitriol liposomes were delivered together with 2.5mim /calcitriol liposomes, disease protection was not observed and the regulatory effect of 2.5mim /calcitriol liposomes was abrogated. Thus, tolerogenic liposomes that target either a dominant CD8+ or a CD4+ T-cell islet epitope can delay diabetes progression but combining multiple epitopes does not enhance protection.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 1
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Immunol Cell Biol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Australia