title: Islet inflammation and CXCL10 in recent-onset type 1 diabetes.
abstract: Type 1 diabetes results from a T cell-mediated destruction of insulin-producing pancreatic beta cells. Little is known on local factors contributing to migration of T cells to pancreatic tissue. We recently demonstrated evidence of viral infection in beta cells in several recent-onset type 1 diabetes patients. Islet inflammation was analysed in a series of new- or recent-onset type 1 diabetic patients and non-diabetic control subjects. Autoimmune T cell reactivity was studied in lymphocytes derived from pancreas-draining lymph nodes of one recent-onset type 1 diabetes patient in partial clinical remission. Insulitic lesions were characterized by presence of beta cells, elevated levels of the chemokine CXCL10 and infiltration of lymphocytes expressing the corresponding chemokine receptor CXCR3 in all pancreatic lesions of type 1 diabetes patients, regardless of enterovirus infection of beta cells. CXCR3 and CXCL10 were undetectable in pancreata of non-diabetic control subjects. T cells isolated from draining lymph nodes of a recent-onset patient with virally infected beta cells and in clinical remission reacted with multiple islet autoantigens and displayed a mixed interferon (IFN)-gamma/interleukin (IL)-10 cytokine pattern. Our data point to CXCL10 as an important cytokine in distressed islets that may contribute to inflammation leading to insulitis and beta cell destruction, regardless of local viral infection. We demonstrate further pro- and anti-inflammatory islet autoreactivity, indicating that different adaptive and innate immune responses may contribute to insulitis and beta cell destruction.
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: B O
authors.initials: BO
authors.lastname: Roep
authors.forename: F S
authors.initials: FS
authors.lastname: Kleijwegt
authors.forename: A G S
authors.initials: AG
authors.lastname: van Halteren
authors.forename: V
authors.initials: V
authors.lastname: Bonato
authors.forename: U
authors.initials: U
authors.lastname: Boggi
authors.forename: F
authors.initials: F
authors.lastname: Vendrame
authors.forename: P
authors.initials: P
authors.lastname: Marchetti
authors.forename: F
authors.initials: F
authors.lastname: Dotta
mesh_terms: D000293:Adolescent; D000328:Adult; D054357:Chemokine CXCL10 / Q000276:immunology*; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000628:therapy / Q000821:virology; D004770:Enterovirus / Q000276:immunology; D004769:Enterovirus Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007249:Inflammation / Q000276:immunology / Q000628:therapy / Q000821:virology; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D054367:Receptors, CXCR3 / Q000276:immunology*; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; C508609:IL10 protein, human; D054367:Receptors, CXCR3; D016753:Interleukin-10; D007371:Interferon-gamma