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Immunology of β-Cell Destruction

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The Islets of Langerhans

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

Abstract

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.

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Abbreviations

APC:

Antigen-presenting cells

BB:

Bio breeding

BCR:

B-cell receptor

CTL:

Cytotoxic T lymphocytes

CTLA-4:

Cytolytic T lymphocyte-associated antigen

cTreg:

Conventional regulatory T

DC:

Dendritic cells

Fas-L:

Fas-Ligand

FoxP3:

Forkhead–winged helix

GABA:

Gamma-amino-butyric acid

GAD:

Glutamic acid decarboxylase

HLA:

Histocompatibility antigens

HSP:

Heat-shock protein

IA-2:

Insulinoma-associated antigen-2

IAA:

Insulin autoantibodies

ICAM:

Intercellular adhesion molecule

IDO:

Indoleamine 2,3-dioxygenase

IFN:

Interferon

ICA:

Islet cell antibodies

ICSA:

Islet cell surface antibodies

IL:

Interleukin

iVEC:

Islet vascular endothelial cells

LFA-1:

Leukocyte function-associated antigen-1

NF:

Nuclear factor

NK:

Natural killer lymphocyte

NKT:

Natural killer T

NO:

Nitric oxide

NOD:

Non obese diabetic

nTreg:

Natural regulatory T

PBMC:

Peripheral blood mononuclear cells

PD-1:

Programmed death-1

pDC:

Plasmacytoid dendritic cell

pLN:

Pancreatic lymph node

pMHC:

Peptide-MHC

PRR:

Pattern recognition receptors

TCR:

T-cell receptor

TEDDY study:

The environmental determinants of diabetes in the young

TF:

Transcription factor

TGF:

Transforming growth factor

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

Treg:

Regulatory T cell

TSA:

Tissue-specific antigen

VNTR:

Variable nucleotide tandem repeat

ZnT8t:

Zinc transporter isoform-8

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  1. Lund University, CRC, Department of Clinical Sciences, University Hospital MAS, SE-205 02, Malmö, Sweden

    Daria La Torre

  2. Lund University, CRC, Department of Clinical Sciences, University Hospital MAS, Entrance 72, building 91, Floor 10, SE-205 02, Malmö, Sweden

    Åke Lernmark

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    Md. Shahidul Islam

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La Torre, D., Lernmark, Å. (2010). Immunology of β-Cell Destruction. In: Islam, M. (eds) The Islets of Langerhans. Advances in Experimental Medicine and Biology, vol 654. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3271-3_24

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