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 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-gamma-producing cells and Ab responses, whereas APC-specific gene expressions led to moderate CTL and IFN-gamma-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.
Cho
J H
JH
National Research Laboratory of DNA Medicine, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Hyojadong, Pohang, Kyungbuk, Korea.
Youn
J W
JW
Sung
Y C
YC
D019264:Adoptive Transfer; D000818:Animals; D019470:Biolistics / Q000379:methods*; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007114:Immunization; D007136:Immunoglobulins / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D053547:Keratin-14; D007633:Keratins / Q000235:genetics; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011401:Promoter Regions, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation; D014758:Viral Core Proteins / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; C507540:KRT14 protein, human; D053547:Keratin-14; C507446:Krt14 protein, mouse; D016177:Macrophage-1 Antigen; D014758:Viral Core Proteins; D007633:Keratins; D007371:Interferon-gamma; D010047:Ovalbumin