Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Marked Expansion of CD11c+CD8+ T-Cells in Melanoma-bearing Mice Induced by Anti-4-1BB Monoclonal Antibody

  • Ju, Seong-A (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan) ;
  • Park, Sang-Min (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan) ;
  • Lee, Sang-Chul (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan) ;
  • Kwon, Byoung S. (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan) ;
  • Kim, Byung-Sam (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
  • Received : 2007.01.12
  • Accepted : 2007.06.01
  • Published : 2007.08.31
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Abstract

4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily, is expressed on activated T-cells, and 4-1BB signaling due to interaction with 4-1BB ligand or ligation with anti-4-1BB monoclonal antibody (mAb) costimulates T cells. It has been shown that administration of anti-4-1BB mAb induces anti-tumor immunity in mice, but the nature of the cellular subsets responsible for this immunity is uncertain. In this study we found that anti-4-1BB mAb administration to B16F10 melanoma-bearing mice induced marked expansion of $CD11c^+CD8^+$ T-cells in parallel with suppression of pulmonary tumors. The mAb-treated mice produced higher levels of $IFN-{\gamma}$ in their tumor tissues, spleen and lymph nodes than mice exposed to control antibody. When the $CD11c^+CD8^+$ T-cells were purified and re-stimulated in vitro, they produced high levels of the Th1 cytokines, $IFN-{\gamma}$ and IL-2, but low levels of the Th2 cytokines, IL-4 and IL-10. Furthermore, they expressed high levels of 4-1BB and CD107a, a marker of activated cytotoxic T-lymphocytes. Our results suggest that $CD11c^+CD8^+$ T-cells play a role in the anti-tumor immunity induced by anti-4-1BB mAb.

Keywords

Acknowledgement

Supported by : University of Ulsan, Korea Research Foundation

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