Molecules and Cells

  • 제24권1호
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  • Pages.132-138
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  • 2007
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
권호 표지

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)
  • 투고 : 2007.01.12
  • 심사 : 2007.06.01
  • 발행 : 2007.08.31
⟨ 이전 논문 다음 논문 ⟩

초록

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.

키워드

과제정보

연구 과제 주관 기관 : University of Ulsan, Korea Research Foundation

참고문헌

  1. Alleva, D. G.., Burger, C. J., and Elgert, K. D. (1994) Tumorinduced regulation of suppressor macrophage nitric oxid and TNF-alpha production. Role of tumor-derived IL-10, TGFbeta, and prostaglandin E2. J. Immunol. 153, 1674−1686
  2. Betts, M. R., Brenchley, J. M., Price, D. A., De Rosa, S. C., Douek, D. C., et al. (2003) Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation. J. Immunol. Methods 281, 65-78 https://doi.org/10.1016/S0022-1759(03)00265-5
  3. Boon, T., De Plaen, E., Lurquin, C., Van den Eynde, B., and van der Bruggen, P. (1992) Identification of tumor rejection antigens recognized by T lymphocytes. Cancer Surv. 13, 23-37
  4. Chang, S. K., Park, B., Shin, J., Ahn, J. H., Kim, I. H., et al. (2002) Proto-oncogene PML enhances antigen presentation by MHC class I molecules in human lung cancer cells. Mol. Cells 14, 130-135
  5. Ghosh, P., Komschlies, K. L., Cippitelli, M., Longo, D. L., Subleski, J., et al. (1995) Gradual loss of T-helper 1 populations in spleens of mice during progressive tumor growth. J. Nat. Cancer Inst. 87, 1478-1483 https://doi.org/10.1093/jnci/87.19.1478
  6. Huleatt, J. W. and Lefrancois, L. (1995) Antigen-driven induction of CD11c on intestinal intraepithelial lymphocytes and $CD8^{+}$ T cells in vivo. J. Immunol. 154, 5684-5693
  7. Jang, I. K., Lee, Z. H., Kim, H. H., Hill, J. M., Kim J. D., et al. (2001) A Novel leucine-rich repeat protein (LRR-1): Potential involvement in 4-1BB-mediated signal transduction. Mol. Cells 12, 304-312
  8. Jang, Y. J., Nam, S. Y., Kim, M. S., Seong, R. H., Park, Y. S., et al. (2002) Simultaneous expression of allogenic class II MHC and B7.1 (CD80) molecules in A20 B-lymphoma cell line enhances tumor immunogenicity. Mol. Cells 13, 130-136
  9. Ju, S. A., Lee, S. C., Kwon, T. H., Heo, S. K., Park, S. M., et al. (2005) Immunity to melanoma mediated by 4-1BB is associated with enhanced activity of tumour-infiltrating lymphocytes. Immunol. Cell Biol. 83, 344-351 https://doi.org/10.1111/j.1440-1711.2005.01330.x
  10. Kim, Y. H., Seo, S. K., Choi, B. K., Kang, W. J., Kim, C. H., et al. (2005) 4-1BB costimulation enhances HSV-1-specific $CD8^{+}$ T cell responses by the induction of $CD11c^{+}CD8^{+}$ T cells. Cell. Immunol. 238, 76-86
  11. Kiertscher, S. M., Luo, J., Dubinett, S. M., and Roth, M. D. (2000) Tumors promote altered maturation and early apoptosis of monocyte-derived dendritic cells. J. Immunol. 164, 1269-1276 https://doi.org/10.4049/jimmunol.164.3.1269
  12. Kobayashi, M., Kobayashi, H., Pollard, R. B., and Suzuki, F. (1998) A pathogenic role of Th2 cells and their cytokine products on the pulmonary metastasis of murine B16 melanoma. J. Immunol. 160, 5869-5873
  13. Li, Q., Carr, A., Ito, F., Teitz-Tennenbaum, S., and Chang, A. E. (2003) Polarization effects of 4-1BB during CD28 costimulation in generating tumor-reactive T cells for cancer immunotherapy. Cancer Res. 63, 2546-2552
  14. Maeda, H. and Shiraishi, A. (1996) TGF-beta contributes to the shift toward Th2-type responses through direct and IL-10-mediated pathways in tumor-bearing mice. J. Immunol. 156, 73-78
  15. Melero, I., Shuford, W. W., Newby, S. A., Aruffo, A., Ledbetter, J. A., et al. (1997) Monoclonal antibodies against the 4-1BB T-cell activation molecule can eradicate established tumors. Nat. Med. 3, 682-685 https://doi.org/10.1038/nm0697-682
  16. McAdam, A. J., Pulaski, B. A., Harkins, S. S., Hutter, E. K., Lord, E. M., et al. (1995) Synergistic effects of co-expression of the Th1-cytokines IL-2 and IFN-gamma on generation of murine tumor-reactive cytotoxic cells. Int. J. Cancer. 61, 628-634 https://doi.org/10.1002/ijc.2910610508
  17. Miller, R. E., Jones, J., Le, T., Whitmore, J., Boiani, N., et al. (2002) 4-1BB-specific monoclonal antibody promotes the generation of tumor-specific immune responses by direct activation of CD8 T cells in a CD40-dependent manner. J. Immunol. 169, 1792-800
  18. Park, E. K., Soh, B. Y., Jang, Y. S., Park, J. H., and Chung, G. H. (2001) Immune induction and modulation in mice following immunization with DNA encoding F protein of respiratory syncytial virus. Mol. Cells 12, 50-56
  19. Pulendran, B., Lingappa, J., Kennedy, M. K., Smith, J., Teepe, M., et al. (1997) Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice. J. Immunol. 159, 2222-2231
  20. Seo, S. K., Choi, J. H., Kim, Y. H., Kang, W. J., Park, H. Y., et al. (2004) 4-1BB-mediated immunotherapy of rheumatoid arthritis. Nat. Med. 10, 1088-1094
  21. Taraban, V. Y., Rowley, T. F., O'Brien, L., Chan, H. T., Haswell, L. E., et al. (2002) Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4-1BB), and their role in the generation of anti-tumor immune responses. Eur. J. Immunol. 32, 3617-3627 https://doi.org/10.1002/1521-4141(200212)32:12<3617::AID-IMMU3617>3.0.CO;2-M
  22. Vinay, D. S. and Kwon, B.S. (1998) Role of 4-1BB in immune responses. Semin. Immunol. 10, 481-489
  23. Weber, J. S. and Rosenberg, S. A. (1998) Modulation of murine tumor major histocompatibility antigens by cytokines in vivo and in vitro. Cancer Res. 48, 5818-5824
  24. Wilcox, R. A., Flies D. B., Zhu, G.., Johnson, A. J., Tamada, K., et al. (2002) Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors. J. Clin. Invest. 109, 651-659 https://doi.org/10.1172/JCI0214184
  25. Yu, P., lee, Y., Liu, W., Krausz, T., Chong, A., et al. (2005) Intratumor depletion of $CD4^{+}$ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. JEM 201, 779-791 https://doi.org/10.1084/jem.20041684