Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients

Coppieters, Ken; Dotta, Francesco; Amirian, Natalie; Campbell, Peter D.; Kay, Thomas; Atkinson, Mark A.; Roep, Bart O.; Herrath, Matthias G. von

doi:10.1084/jem.20111187

Cited by 575 publications

(634 citation statements)

References 36 publications

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“…It is commonly assumed that type 1 diabetes becomes clinically apparent when the remaining beta cell mass (BCM) has decreased to 5-20% [2,3]. Recent studies, however, suggest that patients with type 1 diabetes may still have a large amount of remaining beta cells [4]; in some patients loss of BCM was less than 50% [5]. Moreover, some patients newly diagnosed with type 1 diabetes who underwent autologous nonmyeloablative haematopoietic stem cell transplantation became insulin-independent for several months, suggesting restored function of existing beta cells [6].…”

Section: Introductionmentioning

confidence: 99%

Non-invasive quantification of the beta cell mass by SPECT with 111In-labelled exendin

et al. 2014

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Aims/hypothesis A reliable method for in vivo quantification of pancreatic beta cell mass (BCM) could lead to further insight into the pathophysiology of diabetes. The glucagonlike peptide 1 receptor, abundantly expressed on beta cells, may be a suitable target for imaging. We investigated the potential of radiotracer imaging with the GLP-1 analogue exendin labelled with indium-111 for determination of BCM in vivo in a rodent model of beta cell loss and in patients with type 1 diabetes and healthy individuals. MethodsThe targeting of 111 In-labelled exendin was examined in a rat model of alloxan-induced beta cell loss. Rats were injected with 15 MBq 111 In-labelled exendin and single photon emission computed tomography (SPECT) acquisition was performed 1 h post injection, followed by dissection, biodistribution and ex vivo autoradiography studies of pancreatic sections. BCM was determined by morphometric analysis after staining with an anti-insulin antibody. For clinical evaluation SPECT was acquired 4, 24 and 48 h after injection of 150 MBq 111 In-labelled exendin in five patients with type 1 Maarten Brom and Wietske Woliner-van der Weg contributed equally to this study. Diabetologia (2014) 57:950-959 DOI 10.1007 diabetes and five healthy individuals. The tracer uptake was determined by quantitative analysis of the SPECT images. Results In rats, 111 In-labelled exendin specifically targets the beta cells and pancreatic uptake is highly correlated with BCM. In humans, the pancreas was visible in SPECT images and the pancreatic uptake showed high interindividual variation with a substantially lower uptake in patients with type 1 diabetes. Conclusions/interpretation These studies indicate that 111 Inlabelled exendin may be suitable for non-invasive quantification of BCM.

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Section: Introductionmentioning

confidence: 99%

Non-invasive quantification of the beta cell mass by SPECT with 111In-labelled exendin

et al. 2014

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“…Moreover, infiltrating leucocytes are often found only in the islet periphery (peri-insulitis). Although islet-autoreactive CD8 + T cells were detected [3], the level of insulitis remains surprisingly mild, even in patients with recent-onset type 1 diabetes and death due to ketoacidosis [4]. This picture is complicated by background infiltration in the exocrine pancreas, partly due to peri-mortem changes, with the highest levels of infiltration observed in young patients after prolonged life support [5].…”

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confidence: 99%

What is the role of autoimmunity in type 1 diabetes? A clinical perspective

2014

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Despite tremendous research efforts, type 1 diabetes is one of the few remaining autoimmune diseases without any approved immunological treatment. This observation compels us to reconsider the role of autoimmunity in the pathogenesis of this disease. In this commentary, we will review solely human data in an attempt to appreciate, in an unbiased manner, the importance and relevance of the immunological alterations in patients with type 1 diabetes. The aim of this paper is to generate reflection on this topic, rather than a controversy.

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“…The presence of CD8 + T cells and MHC class I hyperexpression in frozen pancreas tissue samples has been demonstrated in both newly-diagnosed and longstanding T1D patients. The use of in situ tetramer staining shows that some of these cells are specific for islet antigens (Coppieters et al 2012). A recent study using flow cytometry and tetramer staining shows that the frequency of beta-cell-specific CD8 T cells is similar between T1D patients and healthy donors; however, in patients, molecular analysis shows highly skewed oligoclonal TCR repertoires, a sign of chronic autoantigen exposure (Skowera et al 2015).…”

Section: Cytotoxic Cd8 T Lympochytes: Are They Regulatory?mentioning

confidence: 99%

Apportioning Blame: Autoreactive CD4+ and CD8+ T Cells in Type 1 Diabetes

Varela-Calviño

Calviño-Sampedro

Gómez-Touriño

et al. 2017

Arch. Immunol. Ther. Exp.

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Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients

Abstract: In situ tetramer staining reveals the presence of islet antigen-reactive CD8+ T cells in pancreatic islets from deceased type 1 diabetes patients.

Cited by 575 publications

References 36 publications

Non-invasive quantification of the beta cell mass by SPECT with 111In-labelled exendin

Non-invasive quantification of the beta cell mass by SPECT with 111In-labelled exendin

What is the role of autoimmunity in type 1 diabetes? A clinical perspective

Apportioning Blame: Autoreactive CD4+ and CD8+ T Cells in Type 1 Diabetes

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