The timing of GM-CSF expression plasmid administration influences the Th1/Th2 response induced by an HIV-1-specific DNA vaccine

The mechanism of immune activation induced by a plasmid-encoding GM-CSF (pG M-CSF), administered in combination with a DNA vaccine encoding the envelop e of HIV, was studied. Injecting pGM-CSF i.m. into mice 3 days before DNA v accination primarily induced a Th2 response. Simultaneous administration of the DNA vaccine plus pGM-CSF activated both a Th1 and a Th2 response. When the plasmid was injected 3 days after DNA vaccination, enhancement of Th1 immunity predominated. These results suggest that the timing of cytokine ex pression determines the phenotype of the resultant Th response. After 3 day s of pGM-CSF injection, the increased percentages of CD11c(+), CD8(+) cells were observed in the regional lymph nodes. In addition, many infiltrated c ells, including S-100 protein-positive cells, were found in the pGM-CSF-inj ected tissue. The importance of these S-100(+) cells or both CD8(+) and CD1 1c(+) cells, especially that of dendritic cells (DCs), was also studied. DC s derived from bone marrow and cultured in RPMI 1640 medium containing IL-4 and GM-CSF were incubated with DNA vaccine and then transferred into naive mice. Mice receiving DCs showed strong HIV-1-specific Th2 immune responses . Our results suggest that DCs play important roles in the activation or mo dification of the Th2-type immune response induced by DNA vaccination.