Author:
Luce Sandrine,Guinoiseau Sophie,Gadault Alexis,Letourneur Franck,Nitschke Patrick,Bras Marc,Vidaud Michel,Charneau Pierre,Larger Etienne,Colli Maikel L.,Eizirik Decio L.,Lemonnier François,Boitard Christian
Abstract
To circumvent the limitations of available preclinical models for the study of type 1 diabetes (T1D), we developed a new humanized model, the YES-RIP-hB7.1 mouse. This mouse is deficient of murine major histocompatibility complex class I and class II, the murine insulin genes, and expresses as transgenes the HLA-A*02:01 allele, the diabetes high-susceptibility HLA-DQ8A and B alleles, the human insulin gene, and the human co-stimulatory molecule B7.1 in insulin-secreting cells. It develops spontaneous T1D along with CD4+ and CD8+ T-cell responses to human preproinsulin epitopes. Most of the responses identified in these mice were validated in T1D patients. This model is amenable to characterization of hPPI-specific epitopes involved in T1D and to the identification of factors that may trigger autoimmune response to insulin-secreting cells in human T1D. It will allow evaluating peptide-based immunotherapy that may directly apply to T1D in human and complete preclinical model availability to address the issue of clinical heterogeneity of human disease.
Funder
Agence Nationale de la Recherche
European Foundation for the Study of Diabetes
Fonds National de la Recherche Luxembourg
Innovative Medicines Initiative
Subject
Immunology,Immunology and Allergy
Cited by
5 articles.
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