Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Racine, JJ; Misherghi, A; Dwyer, JR; Maser, R; Forte, E; Bedard, O; Sattler, S; Pugliese, A; Landry, L; Elso, C; Nakayama, M; Mannering, S; Rosenthal, N; Serreze, DV.
HLA-DQ8 Supports Development of Insulitis Mediated by Insulin-Reactive Human TCR-Transgenic T Cells in Nonobese Diabetic Mice.
J Immunol. 2023; 211(12):1792-1805 Doi: 10.4049/jimmunol.2300303 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Co-authors Med Uni Graz

Sattler Susanne

Altmetrics:

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Abstract:

In an effort to improve HLA-"humanized" mouse models for type 1 diabetes (T1D) therapy development, we previously generated directly in the NOD strain CRISPR/Cas9-mediated deletions of various combinations of murine MHC genes. These new models improved upon previously available platforms by retaining β2-microglobulin functionality in FcRn and nonclassical MHC class I formation. As proof of concept, we generated H2-Db/H2-Kd double knockout NOD mice expressing human HLA-A*0201 or HLA-B*3906 class I variants that both supported autoreactive diabetogenic CD8+ T cell responses. In this follow-up work, we now describe the creation of 10 new NOD-based mouse models expressing various combinations of HLA genes with and without chimeric transgenic human TCRs reactive to proinsulin/insulin. The new TCR-transgenic models develop differing levels of insulitis mediated by HLA-DQ8-restricted insulin-reactive T cells. Additionally, these transgenic T cells can transfer insulitis to newly developed NSG mice lacking classical murine MHC molecules, but expressing HLA-DQ8. These new models can be used to test potential therapeutics for a possible capacity to reduce islet infiltration or change the phenotype of T cells expressing type 1 diabetes patient-derived β cell autoantigen-specific TCRs.

Find related publications in this database (using NLM MeSH Indexing)

Humans - administration & dosage

Mice - administration & dosage

Animals - administration & dosage

Mice, Inbred NOD - administration & dosage

Diabetes Mellitus, Type 1 - genetics, therapy

Insulin - administration & dosage

Mice, Transgenic - administration & dosage

Diabetes Mellitus, Experimental - administration & dosage

Mice, Knockout - administration & dosage

Receptors, Antigen, T-Cell - genetics

HLA-DQ Antigens - administration & dosage

© Med Uni Graz • Imprint