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International Immunology, Vol. 12, No. 6, 825-832, June 2000
© 2000 Japanese Society for Immunology

Dendritic cells at a DNA vaccination site express the encoded influenza nucleoprotein and prime MHC class I-restricted cytolytic lymphocytes upon adoptive transfer

Adrian Bot1,4, Alexandru C. Stan1,5, Kayo Inaba2, Ralph Steinman3 and Constantin Bona1

1 Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA
2 Laboratory of Immunology, Department of Zoology, Faculty of Science, Kyoto University, Kyoto, Japan
3 Laboratory of Cell Biology and Immunology, Rockefeller University, New York, NY 10021, USA

Correspondence to: A. Bot, Department of Exploratory Biological Research, Alliance Pharmaceutical Corp., 6175 Lusk Boulevard, San Diego, CA 92121, USA

Intradermal inoculation of plasmids expressing antigens that contain MHC class I-restricted epitopes leads to the induction of specific CD8+ cytotoxic T lymphocytes (CTL). The role of in situ transfected antigen-presenting cells (APC) in the priming of specific CTL subsequent to intradermal DNA immunization was investigated using a plasmid (NPV1) expressing the nucleoprotein (NP) of influenza virus that contains a nuclear targeting signal and a dominant class I/Kd-restricted epitope. Inoculation of NPV1 leads to in situ transfection of MHC class II+ and class II cells, as revealed by the nuclear localization of NP. Between 2 and 3% of MHC class II+ and class II cells with the ability to migrate out of the epidermis expressed NP. Upon adoptive transfer into naive recipients, class II+ migratory cells recovered from the area inoculated with NP-expressing plasmid were significantly superior regarding the ability to prime virus-specific CTL as compared to MHC class II cells. Together, these results are consistent with the role of local dendritic cells loaded with antigen in the priming of CTL by intradermal DNA immunization.

Keywords: adoptive transfer, cytotoxic cells, dendritic cells, DNA vaccination, nucleoprotein

4 Present address: Alliance Pharmaceutical Corp., San Diego, CA 92121, USA

5 Present address: Institute of Neuropathology, Hannover Medical School, 30625 Hannover, Germany

Transmitting editor: Z. Ovary


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