Immunology of β-Cell Destruction

Part of the Advances in Experimental Medicine and Biology book series (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.

Keywords

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

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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Copyright information

© 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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