Harnessing memory adaptive regulatory T cells to control autoimmunity in type 1 diabetes

J Mol Cell Biol. 2012 Feb;4(1):38-47. doi: 10.1093/jmcb/mjr040. Epub 2011 Nov 24.

Abstract

Type 1 diabetes (T1D) results from autoimmune destruction of insulin-producing β-cells in the pancreatic islets. There is an immediate need to restore both β-cell function and immune tolerance to control disease progression and ultimately cure T1D. Currently, there is no effective treatment strategy to restore glucose regulation in patients with T1D. FoxP3-expressing CD4(+) regulatory T cells (Tregs) are potential candidates to control autoimmunity because they play a central role in maintaining self-tolerance. However, deficiencies in either naturally occurring Tregs (nTregs) themselves and/or their ability to control pathogenic effector T cells have been associated with T1D. Here, we hypothesize that nTregs can be replaced by FoxP3(+) adaptive Tregs (aTregs), which are uniquely equipped to combat autoreactivity in T1D. Unlike nTregs, aTregs are stable and provide long-lived protection. In this review, we summarize the current understanding of aTregs and their potential for use as an immunological intervention to treat T1D.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adoptive Transfer
  • Animals
  • Autoimmunity*
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / therapy*
  • Disease Progression
  • Forkhead Transcription Factors / immunology
  • Humans
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / pathology
  • Integrin beta Chains / immunology
  • Interleukin-2 / immunology
  • Mice
  • Self Tolerance
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / immunology

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Integrin beta Chains
  • Interleukin-2
  • Transforming Growth Factor beta
  • integrin beta7