INDUCTION OF PERIPHERAL CD8(-CELL TOLERANCE BY CROSS-PRESENTATION OF SELF-ANTIGENS() T)

There is now convincing evidence that CD8(+) T cells can be activated by professional antigen-presenting cells which present antigens derive d from non-lymphoid tissues in association with MHC class I molecules in the draining lymph nodes. This mechanism, referred to as cross-pres entation, enables the immune system to respond to those microorganisms that infect only non-lymphoid tissues. Consistent with this view cros s-presentation was found to focus on antigens expressed in high concen trations and chose released from dying cells, which can be expected to result from viral infections. Recent evidence, however, demonstrates that high dose self antigens can be cross-presented constitutively res ulting in the activation of autoreactive CD8(+) T cells. This does not lead to autoimmunity under physiologic conditions, but to CD95-mediat ed deletion of the T cells. Cross-presentation can thus engage a well- defined pathway of antigen-induced T-cell death and purge the immune s ystem of autoreactive CD8(+) T cells. Low dose self antigens are not c ross-presented and are consequently ignored. The immune system therefo re uses two strategies co avoid CD8(+) T-cell-mediated autoimmunity in the periphery: deletion of autoreactive CD8(+) T cells responding to high dose self antigens and ignorance of self antigens expressed at lo w concentrations.