In situ analysis of pancreatic islets in rats developing diabetes. Appearance of nonendocrine cells with surface MHC class II antigens and cytoplasmic insulin immunoreactivity.

Veld, Pieter In 'T; Pipeleers, Daniël

doi:10.1172/jci113669

Cited by 40 publications

(15 citation statements)

References 16 publications

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“…Our own studies indicate no evidence for aberrant expression of MHC class I1 on p cells in our transfer mice or in our analysis of diabetic female or nondiabetic male NOD mice. MQ, containing immunoreactive insulin were observed in our studies and those of others, indeed, In't Veld and Pipeleers [49] have shown by electron microscopy that the MHC class 11-expressing cells containing insulin were MQ, and dendritic cells. This may provide an explanation of the previous findings based on the detection of class 11-bearing cells containing immunoreactive insulin.…”

Section: Discussionsupporting

confidence: 88%

Characterization of pancreatic islet cell infiltrates in NOD mice: effect of cell transfer and transgene expression

O’Reilly¹,

Hutchings²,

Crocker

et al. 1991

Eur J Immunol

120

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Insulin-dependent diabetes mellitus can be transferred into young irradiated non-obese diabetic (NOD) mice by spleen cells from a diabetic NOD donor. T cells (both L3T4+ and Ly-2+) enter the pancreas 2 weeks following transfer. They are present initially at peri-islet locations but progressively infiltrate the islet with accompanying beta cell destruction. The infiltrate is heterogeneous with respect to V beta usage. Inflammatory macrophages (Mac-1+, F4/80+) can be detected at peri-islet locations at 1 week after transfer and continue to be recruited during the disease process. Their presence at the initiation of disease suggests that their primary function may be autoantigen presentation. Increased expression of major histocompatibility complex (MHC) class I molecules is observed on both endocrine and exocrine tissue in areas of intra-islet infiltration. MHC class II and ICAM-1 expression was restricted to the cells constituting the inflammatory infiltrate. Expression of these molecules was not observed on beta cells implying that presentation of autoantigen by the beta cell itself does not play a role in the beta cell destruction in NOD mice.

show abstract

Section: Discussionsupporting

confidence: 88%

Characterization of pancreatic islet cell infiltrates in NOD mice: effect of cell transfer and transgene expression

O’Reilly¹,

Hutchings²,

Crocker

et al. 1991

Eur J Immunol

120

View full text Add to dashboard Cite

show abstract

“…Our study compares changes in the islet cell structure and composition among three different animal models of T1D. While previous studies have focused on the invading cells that surround the islets and the corresponding islets changes early in the onset of the disease [20, 21], the current work focuses on the long-term outcome on the islets for each diabetic rodent model. Analysis of pancreatic islets in autoimmune animal models (BBDR rat and NOD mouse) showed complete loss of insulin producing β -cells.…”

Section: Discussionmentioning

confidence: 99%

Variations in Rodent Models of Type 1 Diabetes: Islet Morphology

Novikova

Smirnova

Rawal

et al. 2013

Journal of Diabetes Research

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Type 1 diabetes (T1D) is characterized by hyperglycemia due to lost or damaged islet insulin-producing β-cells. Rodent models of T1D result in hyperglycemia, but with different forms of islet deterioration. This study focused on 1 toxin-induced and 2 autoimmune rodent models of T1D: BioBreeding Diabetes Resistant rats, nonobese diabetic mice, and Dark Agouti rats treated with streptozotocin. Immunochemistry was used to evaluate the insulin levels in the β-cells, cell composition, and insulitis. T1D caused complete or significant loss of β-cells in all animal models, while increasing numbers of α-cells. Lymphocytic infiltration was noted in and around islets early in the progression of autoimmune diabetes. The loss of lymphocytic infiltration coincided with the absence of β-cells. In all models, the remaining α- and δ-cells regrouped by relocating to the islet center. The resulting islets were smaller in size and irregularly shaped. Insulin injections subsequent to induction of toxin-induced diabetes significantly preserved β-cells and islet morphology. Diabetes in animal models is anatomically heterogeneous and involves important changes in numbers and location of the remaining α- and δ-cells. Comparisons with human pancreatic sections from healthy and diabetic donors showed similar morphological changes to the diabetic BBDR rat model.

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“…Previously published electron microscopic analyses have demonstrated that MHC class II Ag-positive cells in islets contained granule-like structures that are recognized by Abs to insulin (6, 36). This result suggests that intra-islet DCs contain intact Ags taken up from β cells, consistent with our finding with the MIP-GFP reporters.…”

Section: Discussionmentioning

confidence: 99%

Amplification of Autoimmune Response through Induction of Dendritic Cell Maturation in Inflamed Tissues

Melli¹,

Friedman²,

Martin³

et al. 2009

The Journal of Immunology

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Dendritic cells (DCs) are essential in T cell-mediated destruction of insulin-producing ␤ cells in the islets of Langerhans in type 1 diabetes. In this study, we investigated T cell induction of intra-islet DC maturation during the progression of the disease in both autoimmune-prone NOD and resistant C57BL/6 mice. We demonstrated steady-state capture and retention of unprocessed ␤ cellderived proteins by semimature intra-islet DCs in both mouse strains. T cell-mediated intra-islet inflammation induced an increase in CD40 and CD80 expression and processing of captured Ag by resident DCs without inducing the expression of the p40 subunit of IL-12/23. Some of the CD40 high intra-islet DCs up-regulated CCR7, and a small number of CD40 high DCs bearing unprocessed islet Ags were detected in the pancreatic lymph nodes in mice with acute intra-islet inflammation, demonstrating that T cell-mediated tissue inflammation augments migration of mature resident DCs to draining lymph nodes. Our results identify an amplification loop during the progression of autoimmune diabetes, in which initial T cell infiltration leads to rapid maturation of intra-islet DCs, their migration to lymph nodes, and expanded priming of more autoreactive T cells. Therapeutic interventions that intercept this process may be effective at halting the progression of type 1 diabetes.

show abstract

In situ analysis of pancreatic islets in rats developing diabetes. Appearance of nonendocrine cells with surface MHC class II antigens and cytoplasmic insulin immunoreactivity.

Cited by 40 publications

References 16 publications

Characterization of pancreatic islet cell infiltrates in NOD mice: effect of cell transfer and transgene expression

Characterization of pancreatic islet cell infiltrates in NOD mice: effect of cell transfer and transgene expression

Variations in Rodent Models of Type 1 Diabetes: Islet Morphology

Amplification of Autoimmune Response through Induction of Dendritic Cell Maturation in Inflamed Tissues

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