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Immunology of β-Cell Destruction

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Islets of Langerhans, 2. ed.

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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. These events have been examined in spontaneously diabetic mice or rats, but controlled clinical trials have shown that rodent observations cannot always be 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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Acknowledgement

The research in the authors laboratory has been supported by the National Institutes of Health (grant DK63861), Juvenile Diabetes research foundation, the Swedish Research Council, Diabetesfonden, Childhood Diabetes Fund, and Skåne County Council for Research and Development.

Author information

Authors and Affiliations

  1. Department of Clinical Sciences, Lund University, CRC, University Hospital MAS, Entrance 72, building 91, Floor 10, Malmö, Sweden

    Åke Lernmark & Daria LaTorre

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  1. Åke Lernmark
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  2. Daria LaTorre
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Corresponding author

Correspondence to Åke Lernmark .

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Editors and Affiliations

  1. Södersjukhuset, Karolinska Institutet Dept. Clinical Research & Education, Stockholm, Sweden

    Md. Shahidul Islam

Abbreviations

APC

Antigen-presenting cells

BB

Biobreeding

BCR

B-cell receptor

CTLA-4

Cytolytic T-lymphocyte-associated antigen

cTreg

Conventional regulatory T

DC

Dendritic cells

Fas-L

Fas-Ligand

FOXP3

Forkhead–winged helix

GABA

Gamma-aminobutyric acid

GAD

Glutamic acid decarboxylase

HLA

Human leukocyte antigens

HSP

Heat-shock protein

IA-2

Insulinoma-associated antigen-2

IAA

Insulin autoantibodies

ICA

Islet cell antibodies

ICAM

Intercellular adhesion molecule

ICSA

Islet cell surface antibodies

IDO

Indoleamine 2 3-dioxygenase

IFN

Interferon

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

Nonobese 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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© 2014 Springer Science+Business Media Dordrecht

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Lernmark, Å., LaTorre, D. (2014). Immunology of β-Cell Destruction. In: Islam, M. (eds) Islets of Langerhans, 2. ed.. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6884-0_18-2

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  • DOI: https://doi.org/10.1007/978-94-007-6884-0_18-2

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  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-6884-0

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

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