Immunization through dermal delivery of protein-encoding DNA: a role for migratory dendritic cells

The early mechanisms by which DNA-dependent immunization occurs remain poor ly understood. We determined whether intradermal injection of a cytomegalov irus (CMV) promoter-driven plasmid encoding hen egg lysozyme (pCMV:HEL) ind uced sensitization against the encoded protein, and whether cutaneous dendr itic cells (DC) were involved in this sensitization. Both humoral and cellu lar responses to HEL were observed. DC that migrated from skin explant cult ure 3 days after injection of pCMV:HEL DNA contained mRNA encoding HEL. The y induced a 3.5-7-fold increase in [H-3]thymidine incorporation by HEL prot ein-primed CD4(+) T cells compared to that induced by DC from mice injected with control plasmid. DC emigrating from skin explants recovered from pCMV :HEL injected mice also sensitized naive mice after adoptive transfer and i nduced the generation of CTL. Thus following DNA delivery within the dermis , DC can induce primary and secondary immune responses.