Cross-priming as a predominant mechanism for inducing CD8(+) T cell responses in gene gun DNA immunization

DNA immunization induces CD8(+) CTL responses by bone marrow-derived APCs, which are directly transfected with a plasmid DNA and/or acquire Ags from D NA-transfected non-APCs. To investigate the relative contribution of DNA-tr ansfected APCs vs non-APCs to the initiation of CD8(+) T cell responses, we used tissue-specific promoter-directed gene expression and adoptive transf er systems in gene gun DNA immunization. In this study, we demonstrated tha t non-APC-specific gene expressions induced significant CD8(+) CTL and IFN- gamma -producing cells and Ab responses, whereas APC-specific gene expressi ons led to moderate CTL and IFN-gamma -producers, but no Ab responses. Inte restingly, mice immunized with a non-A-PC-specific plasmid induced more rap id, vigorous, and prolonged proliferation of adoptively transferred Ag-spec ific CD8(+) T cells than APC-specific plasmid-immunized mice. In addition, the in vivo proliferative responses elicited by a non-APC-specific plasmid administration were dependent on TA-P, but were independent of CD4(+) T cel l help. Collectively, our results suggest that cross-priming, in which Ags expressed in non-APCs are taken up, processed, and presented by APCs, plays an important role in the initiation, magnitude, and maintenance of CD8(+) T cell responses in gene gun DNA immunization.