Dendritic cell migration limits the duration of CD8+ T-cell priming to peripheral viral antigen.
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.
Schell
Amanda M
AM
Department of Microbiology and Immunology H107, Penn State M. S. Hershey College of Medicine, Hershey, PA 17033, USA.
Granger
Erica L
EL
Koczot
Frank
F
Fischer
Matthew A
MA
Norbury
Christopher C
CC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D003587:Cytomegalovirus / Q000235:genetics; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology; D012867:Skin / Q000276:immunology; D013997:Time Factors; D014758:Viral Core Proteins / Q000276:immunology
D000956:Antigens, Viral; D010446:Peptide Fragments; D014758:Viral Core Proteins; C102366:nucleoprotein (366-374), influenza virus