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Clinical and Developmental Immunology
Volume 2012 (2012), Article ID 485781, 11 pages
Review Article

Positive and Negative Regulation of Cellular Immune Responses in Physiologic Conditions and Diseases

1Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, 1011 Lausanne, Switzerland
2Swiss Vaccine Research Institute, 1011 Lausanne, Switzerland

Received 25 November 2011; Accepted 20 January 2012

Academic Editor: S. Sozzani

Copyright © 2012 S. Viganò et al. 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.


The immune system has evolved to allow robust responses against pathogens while avoiding autoimmunity. This is notably enabled by stimulatory and inhibitory signals which contribute to the regulation of immune responses. In the presence of a pathogen, a specific and effective immune response must be induced and this leads to antigen-specific T-cell proliferation, cytokines production, and induction of T-cell differentiation toward an effector phenotype. After clearance or control of the pathogen, the effector immune response must be terminated in order to avoid tissue damage and chronic inflammation and this process involves coinhibitory molecules. When the immune system fails to eliminate or control the pathogen, continuous stimulation of T cells prevents the full contraction and leads to the functional exhaustion of effector T cells. Several evidences both in vitro and in vivo suggest that this anergic state can be reverted by blocking the interactions between coinhibitory molecules and their ligands. The potential to revert exhausted or inactivated T-cell responses following selective blocking of their function made these markers interesting targets for therapeutic interventions in patients with persistent viral infections or cancer.