title: Detection of vasostatin-1-specific CD8(+) T cells in non-obese diabetic mice that contribute to diabetes pathogenesis.
abstract: Chromogranin A (ChgA) is an antigenic target of pathogenic CD4(+) T cells in a non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D). Vasostatin-1 is a naturally processed fragment of ChgA. We have now identified a novel H2-K(d) -restricted epitope of vasostatin-1, ChgA 36-44, which elicits CD8(+) T cell responses in NOD mice. By using ChgA 36-44/K(d) tetramers we have determined the frequency of vasostatin-1-specific CD8(+) T cells in pancreatic islets and draining lymph nodes of NOD mice. We also demonstrate that vasostatin-1-specific CD4(+) and CD8(+) T cells constitute a significant fraction of islet-infiltrating T cells in diabetic NOD mice. Adoptive transfer of T cells from ChgA 36-44 peptide-primed NOD mice into NOD/severe combined immunodeficiency (SCID) mice led to T1D development. These findings indicate that vasostatin-1-specific CD8(+) T cells contribute to the pathogenesis of type 1 diabetes in NOD mice.
authors.affiliation: Department of Microbiology and Immunology, Centre for Human Immunology.
authors.forename: E
authors.initials: E
authors.lastname: Nikoopour
authors.affiliation: Department of Microbiology and Immunology, Centre for Human Immunology.
authors.forename: O
authors.initials: O
authors.lastname: Krougly
authors.affiliation: Department of Microbiology and Immunology, Centre for Human Immunology.
authors.forename: E
authors.initials: E
authors.lastname: Lee-Chan
authors.affiliation: Department of Microbiology and Immunology, Centre for Human Immunology.
authors.forename: S M
authors.initials: SM
authors.lastname: Haeryfar
authors.affiliation: Department of Microbiology and Immunology, Centre for Human Immunology.|Robarts Research Institute, University of Western Ontario, London, ON, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Singh
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D053379:Chromogranin A / Q000276:immunology / Q000302:isolation & purification*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology*; D018984:Epitopes, T-Lymphocyte; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010446:Peptide Fragments / Q000276:immunology / Q000302:isolation & purification*
chemical_list: D053379:Chromogranin A; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; C064110:vasostatin I
keywords: CD8+ T cells; NOD mice; autoimmunity; chromogranin A; type 1 diabetes; vasostatin-1