Immunology of β-Cell Destruction

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 654)


The pancreatic islet β-cells are the target for an autoimmune process that eventually results in an inability to control blood glucose due to the lack of insulin. The different steps that eventually lead to the complete loss of the β-cells are reviewed to include the very first step of a triggering event that initiates the development of β-cell autoimmunity to the last step of appearance of islet-cell autoantibodies, which may mark that insulitis is about to form. The observations that the initial β-cell destruction by virus or other environmental factors triggers islet autoimmunity not in the islets but in the draining pancreatic lymph nodes are reviewed along with possible basic mechanisms of loss of tolerance to islet autoantigens. Once islet autoimmunity is established the question is how β-cells are progressively killed by autoreactive lymphocytes which eventually results in chronic insulitis. Many of these series of events have been dissected in spontaneously diabetic mice or rats, but controlled clinical trials have shown that rodent observations are not always translated into mechanisms in humans. Attempts are therefore needed to clarify the step 1 triggering mechanisms and the step to chronic autoimmune insulitis to develop evidence-based treatment approaches to prevent type 1 diabetes.


Islet autoimmunity Autoantigens Prediction Prevention Insulitis Islet autoantibodies CD4+ T cells CD8+ T cells T regulatory cells Antigen-presenting cells Dendritic cells 



Antigen-presenting cells


Bio breeding


B-cell receptor


Cytotoxic T lymphocytes


Cytolytic T lymphocyte-associated antigen


Conventional regulatory T


Dendritic cells




Forkhead–winged helix


Gamma-amino-butyric acid


Glutamic acid decarboxylase


Histocompatibility antigens


Heat-shock protein


Insulinoma-associated antigen-2


Insulin autoantibodies


Intercellular adhesion molecule


Indoleamine 2,3-dioxygenase




Islet cell antibodies


Islet cell surface antibodies




Islet vascular endothelial cells


Leukocyte function-associated antigen-1


Nuclear factor


Natural killer lymphocyte


Natural killer T


Nitric oxide


Non obese diabetic


Natural regulatory T


Peripheral blood mononuclear cells


Programmed death-1


Plasmacytoid dendritic cell


Pancreatic lymph node




Pattern recognition receptors


T-cell receptor

TEDDY study

The environmental determinants of diabetes in the young


Transcription factor


Transforming growth factor


Toll-like receptor


Tumor necrosis factor


Regulatory T cell


Tissue-specific antigen


Variable nucleotide tandem repeat


Zinc transporter isoform-8


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© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Lund University, CRC, Department of Clinical SciencesUniversity Hospital MASMalmöSweden
  2. 2.Lund University, CRC, Department of Clinical SciencesUniversity Hospital MASMalmöSweden

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