Cross-presentation: inducing CD8 T cell immunity and tolerance

Abstract.

The term cross-presentation denotes the presentation of exogenous (extracellular) antigens to T cells, particularly CD8 T cells. It permits professional antigen-presenting cells which have collected antigens in nonlymphoid tissues to activate naive CD8 T cells in the secondary lymphatic compartment. Thus it allows CD8 T cells to scan nonlymphoid tissues for pathogens without the need of migrating there themselves and may hence be critical for immune responses to tissue-tropic viruses. It may also be essential in the immune response to nonlymphoid tumors. In contrast to the induction of immunogenic responses to pathogens, cross-presentation of self-antigens leads to CD8 T cell tolerance by deletion of autoreactive CD8 T cells. The precise way in which the immune system distinguishes self from foreign is not known, but modification in the cross-presenting antigen-presenting cell, such as that achieved by CD4 T cell help or inflammatory signals, may play a critical role in this process. If the dose of the self-antigen or the avidity of the T cell receptor is too low, cross-presentation fails to remove autoreactive CD8 T cells. Ignoring the self-antigen, these cells recirculate through the secondary lymphatics, unless they are activated, for example, by a cross-reactive virus. Then autoimmunity may be triggered.