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Clinical and Developmental Immunology
Volume 2011 (2011), Article ID 294968, 9 pages
http://dx.doi.org/10.1155/2011/294968
Review Article

Mechanisms That Regulate Peripheral Immune Responses to Control Organ-Specific Autoimmunity

School of Health Sciences, University of Notre Dame Australia, 19 Mouat Street, Fremantle, WA 6959, Australia

Received 16 January 2011; Accepted 16 February 2011

Academic Editor: Aziz Alami Chentoufi

Copyright © 2011 Gerard F. Hoyne. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The immune system must balance the need to maintain a diverse repertoire of lymphocytes to be able to fight infection with the need to maintain tolerance to self-proteins. The immune system places strict regulation over the ability of T cells to produce the major T cell growth factor interleukin 2 as this cytokine can influence a variety of immune outcomes. T cells require the delivery of two signals, one through the antigen receptor and a second through the costimulatory receptor CD28. The immune system uses a variety of E3 ubiquitin ligases to target signaling proteins that function downstream of the TCR and CD28 receptors. Mutations in these E3 ligases can lead to a breakdown in immune tolerance and development of autoimmunity. This paper will examine the role of a range of E3 ubiquitin ligases and signaling pathways that influence the development of T-cell effector responses and the development of organ-specific autoimmune diseases such as type 1 diabetes.