Maintenance of peripheral tolerance to islet antigens

Emma E Hamilton-Williams; Anne-Sophie Bergot; Peta L S Reeves; Raymond J Steptoe

doi:10.1016/j.jaut.2016.05.009

Maintenance of peripheral tolerance to islet antigens

J Autoimmun. 2016 Aug:72:118-25. doi: 10.1016/j.jaut.2016.05.009. Epub 2016 May 30.

Authors

Emma E Hamilton-Williams¹, Anne-Sophie Bergot², Peta L S Reeves², Raymond J Steptoe²

Affiliations

¹ The University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia. Electronic address: e.hamiltonwilliams@uq.edu.au.
² The University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.

PMID: 27255733
DOI: 10.1016/j.jaut.2016.05.009

Abstract

Reestablishment of immune tolerance to the insulin-producing beta cells is the desired goal for type 1 diabetes (T1D) treatment and prevention. Immune tolerance to multiple islet antigens is defective in individuals with T1D, but the mechanisms involved are multifaceted and may involve loss of thymic and peripheral tolerance. In this review we discuss our current understanding of the varied mechanisms by which peripheral tolerance to islet antigens is maintained in healthy individuals where genetic protection from T1D is present and how this fails in those with genetic susceptibility to disease. Novel findings in regards to expression of neo-islet antigens, non-classical regulatory cell subsets and the impact of specific genetic variants on tolerance induction are discussed.

Keywords: Genetic susceptibility; Regulatory T cells; Tolerance; Type 1 diabetes.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autoantigens / immunology*
Central Tolerance / immunology
Diabetes Mellitus, Type 1 / immunology*
Humans
Insulin-Secreting Cells / immunology*
Models, Immunological
Peripheral Tolerance / immunology*
T-Lymphocytes, Regulatory / immunology
Thymus Gland / immunology

Substances

Autoantigens