KMID : 1235920090010010046
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Medical Journal of Catholoc University of Daegu 2009 Volume.1 No. 1 p.46 ~ p.55
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Lysosomal Targeting of E7 Antigens dose-dependently Elicits Ag-speckfic Th2 Type CC4+ T and Tumor Protective IFN ¥ã+/CD8+ T Cell Responses in an HPV 16 E7 DNA Vaccine model
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Park Byung-Tae
Sin Jeong-Im
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Abstract
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Previously, we reported that targeting of HPV 16 E7 antigens to the lysosomal compartment for the MHC II pathway induced MHC class I-dependent CD8+ CTL responses responsible for antitumor activity in a DNA vaccine model. In this study, we observed that Ag-specific IgG and IgE antibodies were dosedependently induced while IgM production was unaffected. This suggests that vaccine dose is an important factor in escalating a class switch from IgM to IgG and IgE. Moreover, Ag-specific IgG2b and to a lesser degree IgG1 (Th1 type) were dosedependently produced. In contrast, IgG2a (Th1 type) and IgG3 isotypes were not induced. This unique induction pattern of IgG isotypes suggests a Th2 type response. When stimulated in vitro with an E7 antigen, CD4+ T cells of E7-immunized animals produced IL-10 (Th2 type cytokine) but not IFN-¥ã (Th1 type cytokine), suggesting a Th2 type cellular response, whereas Ag-specific IFN-¥ã+/CD8+ T cells and tumor protection were elicited in these animals in a vaccine dose-dependent fashion. These collective data show that lysosomal targeting of an antigen can induce Ag-specific IFN-¥ã+/CD8+ T cell (CTL) responses under Th2 type cytokine environment in this model. This further supports that CD8+ CTL induction is not dependent solely on Th1 type cytokine environments.
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