Positive and Negative Regulation of Cellular Immune Responses in Physiologic Conditions and Diseases
Open Access
- 26 March 2012
- journal article
- review article
- Published by Hindawi Limited in Clinical and Developmental Immunology
- Vol. 2012, 1-11
- https://doi.org/10.1155/2012/485781
Abstract
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.Keywords
Funding Information
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
This publication has 141 references indexed in Scilit:
- 2B4+ CD8+ T cells play an inhibitory role against constrained HIV epitopesBiochemical and Biophysical Research Communications, 2011
- Tumor-infiltrating NY-ESO-1–specific CD8 + T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancerProceedings of the National Academy of Sciences, 2010
- Enhancing SIV-specific immunity in vivo by PD-1 blockadeNature, 2008
- Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infectionNature Immunology, 2008
- Apoptosis Regulators Fas and Bim Cooperate in Shutdown of Chronic Immune Responses and Prevention of AutoimmunityImmunity, 2008
- T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activationNature Immunology, 2008
- Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotypeProceedings of the National Academy of Sciences, 2007
- Heterogeneity and Cell-Fate Decisions in Effector and Memory CD8+ T Cell Differentiation during Viral InfectionImmunity, 2007
- PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infectionThe Journal of Experimental Medicine, 2006
- Co-inhibitory molecules of the B7–CD28 family in the control of T-cell immunityNature Reviews Immunology, 2004