Dendritic Cell Migration Limits the Duration of CD8+T-Cell Priming to Peripheral Viral Antigen

Abstract

CD8(+) T cells (T(CD8(+))) play a crucial role in immunity to viruses. Antiviral T(CD8(+)) are initially activated by recognition of major histocompatibility complex (MHC) class I-peptide complexes on the surface of professional antigen-presenting cells (pAPC). Migration of pAPC from the site of infection to secondary lymphoid organs is likely required during a natural infection. Migrating pAPC can be directly infected with virus or may internalize antigen derived from virus-infected cells. The use of experimental virus infections to assess the requirement for pAPC migration in initiation of T(CD8(+)) responses has proven difficult to interpret because injected virus can readily drain to secondary lymphoid organs without the need for cell-mediated transport. To overcome this ambiguity, we examined the generation of antigen-specific T(CD8(+)) after immunization with recombinant adenoviruses that express antigen driven by skin-specific or ubiquitous promoters. We show that the induction of T(CD8(+)) in response to tissue-targeted antigen is less efficient than the response to ubiquitously expressed antigen and that the resulting T(CD8(+)) fail to clear all target cells pulsed with the antigenic peptide. This failure to prime a fully functional T(CD8(+)) response results from a reduced period of priming to peripherally expressed antigen versus ubiquitously expressed antigen and correlated with a brief burst of pAPC migration from the skin, a requirement for induction of the response to peripheral antigen. These results indicate that a reduced duration of pAPC migration after virus infection likely reduces the amplitude of the T(CD8(+)) response, allowing persistence of the peripheral virus.