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National Research Laboratory of DNA Medicine, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Hyojadong, Pohang, Kyungbuk, Korea
DNA immunization induces CD8+ CTL responses by bone
marrow-derived APCs, which are directly transfected with a plasmid DNA
and/or acquire Ags from DNA-transfected non-APCs. To investigate the
relative contribution of DNA-transfected APCs vs non-APCs to the
initiation of CD8+ T cell responses, we used
tissue-specific promoter-directed gene expression and adoptive transfer
systems in gene gun DNA immunization. In this study, we demonstrated
that non-APC-specific gene expressions induced significant
CD8+ CTL and IFN-
-producing cells and Ab responses,
whereas APC-specific gene expressions led to moderate CTL and
IFN--producers, but no Ab responses. Interestingly, mice immunized
with a non-APC-specific plasmid induced more rapid, vigorous, and
prolonged proliferation of adoptively transferred Ag-specific
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 TAP, but were
independent of CD4+ T cell 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.
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