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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Summary: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.
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ISSN:1939-327X
1939-327X
DOI:10.2337/db14-0549