Peripheral CD8 T-cell responses to apoptotic cell proteins and peptides.

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-beta 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.