Glucagon-reactive islet-infiltrating CD8 T cells in NOD mice

Autor:	Christopher D Bando, Teresa P. DiLorenzo, Rodolfo J. Chaparro, Carla Smith, Gayatri Mukherjee, Jennifer Schloss
Rok vydání:	2015
Předmět:	Enzyme-Linked Immunospot Assay endocrine system Immunology Epitopes T-Lymphocyte Autoimmunity Nod CD8-Positive T-Lymphocytes Biology Proglucagon Autoantigens Glucagon Interferon-gamma Islets of Langerhans Antigen Mice Inbred NOD Cell Line Tumor medicine Animals Immunology and Allergy Cytotoxic T cell NOD mice Pancreatic islets H-2 Antigens Computational Biology Original Articles Disease Models Animal Diabetes Mellitus Type 1 medicine.anatomical_structure Cell culture Cancer research Epitope Mapping Interferon-gamma Release Tests Protein Binding
Zdroj:	Immunology. 144:631-640
ISSN:	0019-2805
DOI:	10.1111/imm.12415
Popis:	Type 1 diabetes is characterized by T-cell-mediated destruction of the insulin-producing β cells in pancreatic islets. A number of islet antigens recognized by CD8 T cells that contribute to disease pathogenesis in non-obese diabetic (NOD) mice have been identified; however, the antigenic specificities of the majority of the islet-infiltrating cells have yet to be determined. The primary goal of the current study was to identify candidate antigens based on the level and specificity of expression of their genes in mouse islets and in the mouse β cell line MIN6. Peptides derived from the candidates were selected based on their predicted ability to bind H-2K(d) and were examined for recognition by islet-infiltrating T cells from NOD mice. Several proteins, including those encoded by Abcc8, Atp2a2, Pcsk2, Peg3 and Scg2, were validated as antigens in this way. Interestingly, islet-infiltrating T cells were also found to recognize peptides derived from proglucagon, whose expression in pancreatic islets is associated with α cells, which are not usually implicated in type 1 diabetes pathogenesis. However, type 1 diabetes patients have been reported to have serum autoantibodies to glucagon, and NOD mouse studies have shown a decrease in α cell mass during disease pathogenesis. Our finding of islet-infiltrating glucagon-specific T cells is consistent with these reports and suggests the possibility of α cell involvement in development and progression of disease.
Databáze:	OpenAIRE
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