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Clinical and Developmental Immunology
Volume 2012 (2012), Article ID 269756, 7 pages
http://dx.doi.org/10.1155/2012/269756
Review Article

Coinhibitory Molecules in Autoimmune Diseases

1Center for Rheumatic Diseases, Saiseikai Narashino Hospital, Narashino 275-8580, Japan
2Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba 260-8670, Japan

Received 9 July 2012; Accepted 21 August 2012

Academic Editor: Timothy B. Niewold

Copyright © 2012 Norihiko Watanabe and Hiroshi Nakajima. 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

Coinhibitory molecules such as CTLA-4, PD-1 and BTLA negatively regulate immune responses. Multiple studies indicate that the deficiency or mutation of coinhibitory molecules leads to the development of autoimmune diseases in mice and humans, indicating that the negative signals from coinhibitory molecules are crucial for the prevention of autoimmunity. In some conditions, the administration of decoy coinhibitory receptors (e.g., CTLA-4 Ig) or mAb against coinhibitory molecules suppresses the responses of self-reactive T cells in autoimmune diseases. Therefore, modulation of coinhibitory signals seems to be an attractive approach to induce tolerance in autoimmune diseases in humans where the disease-inducing self-antigens are not known. Particularly, administration of CTLA-4 Ig has shown great promise in animal models of autoimmune diseases and has been gaining increasing attention in clinical investigation in several autoimmune diseases in humans.