Abstract
There is evidence that the limited immunogenicity of plasmid DNA vaccines is the result, at least in part, of the rapid clearance of vaccine antigen expression by antigen-specific immune responses. However, the cell types responsible for the clearance of plasmid DNA vaccine antigens are not known. Here we demonstrate that macrophages, NK cells, and CD8+ T cells did not significantly contribute to the DNA antigen clearance but CD4+ T cells played the crucial role in attenuating plasmid DNA vaccine antigen expression. Adoptive transfer experiments demonstrate that CD4+ T cells facilitated DNA vaccine antigen clearance in a Fas/FasL-dependent manner. Furthermore, we show that depletion of CD4+ T cells prevented the clearance of vaccine antigen and the appearance of a CD8+ T-cell immune response. Inoculation of major histocompatibility complex class II KO mice with the plasmid DNA led to persistent antigen expression and abolition of a CD8+ T-cell immune response. Importantly, the prolongation of antigen expression by disrupting the CD4+ T-cell Fas/FasL myocytes signaling led to a 3- to 5-fold increase of antigen-specific CD8+ T-cell responses. These data demonstrate a dominant role of CD4+ T cell–mediated cytotoxicity in plasmid DNA vaccine antigen clearance.
CD8+T-cell Activation in Mice Injected with a Plasmid DNA Vaccine Encoding AMA-1 of the Reemerging KoreanPlasmodium vivax
