Cutting edge: Recombinant adenoviruses induce CD8 T cell responses to an inserted protein whose expression is limited to nonimmune cells

CD8 T cells (TCD8+) play a crucial role in immunity to viruses. Current und erstanding of activation of naive T cells entails Ag presentation by profes sional APCs (pAPCs). What happens, however, when viruses evolve to avoid in fecting pAPCs? We have studied the consequences of this strategy by generat ing recombinant adenoviruses that express influenza A virus nucleoprotein u nder the control of tissue-specific promoters. We show that the immunogenic ity of such viruses requires their delivery to organs capable of expressing nucleoprotein. This indicates that infection of pAPCs is not required for adenoviruses to elicit a TCD8+ response, probably due to a cross-priming vi a pAPCs. While this bodes well for recombinant adenoviruses as vaccines, it dims their prospects as gene therapy vectors.