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Critical Reviews™ in Immunology
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ISSN Imprimer: 1040-8401
ISSN En ligne: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v27.i4.50
pages 357-365

Peripheral CD8 T-Cell Responses to Apoptotic Cell Proteins and Peptides

Yu Feng Peng
Rheumatology, University of Washington, Seattle, WA 98195, USA
Keith B. Elkon
Rheumatology and Immunology, University of Washington, Seattle, WA 98195, USA


The immune system must contend with the billions of cells that are turned over on a daily basis; many of these cells derived from the immune system itself. Recent evidence suggests that the apoptotic cells are processed and presented through classical pathways for MHC II presentation to CD4 T cells and also are “cross-presented” through a phagosome-cytosolic pathway or released into the cytosol for presentation to CD8 T cells. It appears that the continuous presentation of self-peptides is required for active maintenance of T-cell tolerance. Although for both CD4 and CD8 T cells, anergy is a dominant pathway for tolerance, presentation of self-peptides to CD8 and CD4 T may induce different responses. Phagocytosis of apoptotic cells leads to the production of TGF-β and/or IL-10 by antigen-presenting cells and there is evidence to suggest that these cytokines favor the generation of CD4 T regulatory cells following encounter with self-antigen. In contrast, CD8 T cells undergo brief activation, an abortive proliferation ultimately leading to reduced long-term survival. The relative quantity and quality of all three signals of TCR engagement, costimulation versus coinhibition and quality of the cytokine response, distinguish T-cell responses to self-versus foreign antigens.

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