Increased immune cell infiltration of the exocrine pancreas: a possible contribution to the pathogenesis of type 1 diabetes

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 be...

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Published in:	Diabetes (New York, N.Y.) Vol. 63; no. 11; p. 3880
Main Authors:	Rodriguez-Calvo, Teresa, Ekwall, Olov, Amirian, Natalie, Zapardiel-Gonzalo, Jose, von Herrath, Matthias G
Format:	Journal Article
Language:	English
Published:	United States 01.11.2014
Subjects:	Adult CD4-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - metabolism Diabetes Mellitus, Type 1 - immunology Diabetes Mellitus, Type 1 - metabolism Diabetes Mellitus, Type 1 - pathology Female Fluorescent Antibody Technique Humans In Vitro Techniques Islets of Langerhans - immunology Islets of Langerhans - metabolism Islets of Langerhans - pathology Male Pancreas, Exocrine - cytology Pancreas, Exocrine - immunology Pancreas, Exocrine - metabolism
ISSN:	1939-327X, 1939-327X
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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.
AbstractList	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.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. 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.
Author	Rodriguez-Calvo, Teresa Amirian, Natalie Zapardiel-Gonzalo, Jose von Herrath, Matthias G Ekwall, Olov
Author_xml	– sequence: 1 givenname: Teresa surname: Rodriguez-Calvo fullname: Rodriguez-Calvo, Teresa organization: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA – sequence: 2 givenname: Olov surname: Ekwall fullname: Ekwall, Olov organization: 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 – sequence: 3 givenname: Natalie surname: Amirian fullname: Amirian, Natalie organization: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA – sequence: 4 givenname: Jose surname: Zapardiel-Gonzalo fullname: Zapardiel-Gonzalo, Jose organization: Freelance consultant, San Diego, CA – sequence: 5 givenname: Matthias G surname: von Herrath fullname: von Herrath, Matthias G email: matthias@liai.org organization: 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
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ContentType	Journal Article
Copyright	2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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Snippet	Type 1 diabetes (T1D) results from a complex interplay between genetic susceptibility and environmental factors that have been implicated in the pathogenesis...
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SubjectTerms	Adult CD4-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - metabolism Diabetes Mellitus, Type 1 - immunology Diabetes Mellitus, Type 1 - metabolism Diabetes Mellitus, Type 1 - pathology Female Fluorescent Antibody Technique Humans In Vitro Techniques Islets of Langerhans - immunology Islets of Langerhans - metabolism Islets of Langerhans - pathology Male Pancreas, Exocrine - cytology Pancreas, Exocrine - immunology Pancreas, Exocrine - metabolism
Title	Increased immune cell infiltration of the exocrine pancreas: a possible contribution to the pathogenesis of type 1 diabetes
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