Dendritic Cell Apoptosis in the Maintenance of Immune Tolerance
- 24 February 2006
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 311 (5764) , 1160-1164
- https://doi.org/10.1126/science.1122545
Abstract
Apoptosis in the immune system is critical for maintaining self-tolerance and preventing autoimmunity. Nevertheless, inhibiting apoptosis in lymphocytes is not alone sufficient to break self-tolerance, suggesting the involvement of other cell types. We investigated whether apoptosis in dendritic cells (DCs) helps regulate self-tolerance by generating transgenic mice expressing the baculoviral caspase inhibitor, p35, in DCs (DC-p35). DC-p35 mice displayed defective DC apoptosis, resulting in their accumulation and, in turn, chronic lymphocyte activation and systemic autoimmune manifestations. The observation that a defect in DC apoptosis can independently lead to autoimmunity is consistent with a central role for these cells in maintaining immune self-tolerance.Keywords
This publication has 28 references indexed in Scilit:
- Requirement for Caspase-8 in NF-κB Activation by Antigen ReceptorScience, 2005
- T Cell–specific Ablation of Fas Leads to Fas Ligand–mediated Lymphocyte Depletion and Inflammatory Pulmonary FibrosisThe Journal of Experimental Medicine, 2004
- Tolerogenic Dendritic CellsAnnual Review of Immunology, 2003
- Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunityGenes & Development, 2003
- Inherited Human Caspase 10 Mutations Underlie Defective Lymphocyte and Dendritic Cell Apoptosis in Autoimmune Lymphoproliferative Syndrome Type IICell, 1999
- MATURE T LYMPHOCYTE APOPTOSIS—Immune Regulation in a Dynamic and Unpredictable Antigenic EnvironmentAnnual Review of Immunology, 1999
- Dendritic Cells Induce Autoimmune Diabetes and Maintain Disease via De Novo Formation of Local Lymphoid TissueThe Journal of Experimental Medicine, 1998
- Targeted Expression of Major Histocompatibility Complex (MHC) Class II Molecules Demonstrates that Dendritic Cells Can Induce Negative but Not Positive Selection of Thymocytes In VivoThe Journal of Experimental Medicine, 1997
- Improved version of a human CD2 minigene based vector for T cell-specific expression in transgenic miceJournal of Immunological Methods, 1995
- Fas and Fas ligand: lpr and gld mutationsImmunology Today, 1995