CONTRIBUTION OF CELLS AT THE SITE OF DNA VACCINATION TO THE GENERATION OF ANTIGEN-SPECIFIC IMMUNITY AND MEMORY

Gene gun-mediated DNA vaccination stimulates an immune response charac terized by the activation of IgG-secreting B cells and IFN-gamma-secre ting T cells, To monitor the contribution of cells at the site of vacc ination to this process, transfected skin was periodically removed and grafted onto naive recipients, Immediate removal of vaccinated skin a brogated the development of an immune response, Low-level IgG producti on was stimulated when the vaccination site was left in place for grea ter than or equal to 5 h, with the strength of this response increasin g the longer the site remained intact (for up to 2 wk), Measurable pri mary T cell responses were observed in animals whose vaccination site remained in place for greater than or equal to 1 day. Skin grafts tran sferred 0 to 24 h postvaccination stimulated a primary immune response in naive recipients, Memory B and T cells were generated in animals w hose site of vaccination remained intact for 5 to 12 h, Skin transferr ed within 12 h of vaccination triggered memory B and T cell developmen t in graft recipients, while the removal of skin > 12 h postvaccinatio n did not reduce memory in vaccinated mice. These findings suggest tha t 1) primary immunity is induced by cells that migrate rapidly from th e site of immunization, 2) nonmigratory cells influence the magnitude of this primary response, and 3) migratory cells alone are responsible for the induction of immunologic memory.