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KMID : 0578320070240010132
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Molecules and Cells
2007 Volume.24 No. 1 p.132 ~ p.138
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Marked Expansion of CD11c+CD8+ T-Cells in Melanoma-bearing Mice Induced by Anti-4-1BB Monoclonal Antibody
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Ju Seong-A
Park Sang-Min
Lee Sang-Chul
Kwon Byoung S.
Kim Byung-Sam
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Abstract
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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-? 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-? 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
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KEYWORD
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4-1BB, Anti-tummor immunity, Melanoma, Th1 cytokines
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