title: Increased immune cell infiltration of the exocrine pancreas: a possible contribution to the pathogenesis of type 1 diabetes.
abstract: Type 1 diabetes (T1D) results from a complex interplay between genetic susceptibility and environmental factors that have been implicated in the pathogenesis of disease both as triggers and potentiators of β-cell destruction. CD8 T cells are the main cell type found in human islets, and they have been shown in vitro to be capable of killing β-cells overexpressing MHC class I. In this study, we report that CD8 T cells infiltrate the exocrine pancreas of diabetic subjects in high numbers and not only endocrine areas. T1D subjects present significantly higher CD8 T cell density in the exocrine tissue without the presence of prominent insulitis. Even T1D donors without remaining insulin-containing islets and long disease duration show elevated levels of CD8 T cells in the exocrine compartment. In addition, higher numbers of CD4(+) and CD11c(+) cells were found in the exocrine tissue. Preliminary data in type 2 diabetic (T2D) subjects indicate that overall, there might be a spontaneous inflammatory infiltration of the exocrine tissue, common to both T1D and T2D subjects. Our study provides the first information on the precise tissue distribution of CD8 T cells in pancreata from T1D, T2D, autoantibody-positive, and healthy control subjects.
authors.affiliation: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rodriguez-Calvo
authors.affiliation: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA Department of Rheumatology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Department of Pediatrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Olov
authors.initials: O
authors.lastname: Ekwall
authors.affiliation: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Amirian
authors.affiliation: Freelance consultant, San Diego, CA.
authors.forename: Jose
authors.initials: J
authors.lastname: Zapardiel-Gonzalo
authors.affiliation: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA Novo Nordisk Diabetes Research & Development Center, Seattle, WA matthias@liai.org.
authors.forename: Matthias G
authors.initials: MG
authors.lastname: von Herrath
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D046790:Pancreas, Exocrine / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*