DOI QR코드

DOI QR Code

Requirement of CD4 Help for Induction of CD8 T Cell Response Specific for Virally Derived H60

  • Ryu, Su-Jeong (Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Kang, Bo-Ra (Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Kim, Seok-Ho (Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Tae-Woo (Graduate School of Medicine, Korea University) ;
  • Chang, Jun (Division of Life and Pharmaceutical Sciences, Ewha Woman's University) ;
  • Choi, Eun-Young (Department of Biomedical Sciences, Seoul National University College of Medicine)
  • Received : 2012.05.09
  • Accepted : 2012.05.29
  • Published : 2012.06.30

Abstract

CD40-CD40L-mediated help from CD4 T cells is essential to induce primary CD8 T cell responses specific to the non-inflammatory cell-based antigen H60. In this study, using H60 as a model antigen, we generated recombinant vaccinia viruses (rVVs) expressing the H60 CD8 epitope and investigated whether CD4 help was required to activate the CD8 T cell response specific to the virally expressed H60. The immune response after infection with rVVs expressing H60 was similar to that after immunization with H60 congenic splenocytes, with a peak frequency of H60-specific CD8 T cells detected in the blood on day 10 post-infection. A CD8 T cell response specific for virally derived H60 was not induced in CD4-depleted mice, but was in CD40-deficient mice. These results provide insights into the characterization of the CD8 T cell response specifically for antigens originating from cellular sources compared to viral sources.

Keywords

References

  1. Kaech S. M., E. J. Wherry, and R. Ahmed. 2002. Effector and memory T-cell differentiation: implications for vaccine development. Nat. Rev. Immunol. 2: 251-262. https://doi.org/10.1038/nri778
  2. Keene, J. A., and J. Forman. 1982. Helper activity is required for the in vivo generation of cytotoxic T lymphocytes. J. Exp. Med. 155: 768-782. https://doi.org/10.1084/jem.155.3.768
  3. Rees, M. A., A. S. Rosenberg, T. I. Munitz, and A. Singer. 1990. In vivo induction of antigen-specific transplantation tolerance to Qa1a by exposure to alloantigen in the absence of T-cell help. Proc. Natl. Acad. Sci. U. S. A. 87: 2765-2769. https://doi.org/10.1073/pnas.87.7.2765
  4. Ryu, S. J., K. M. Jung, H. S. Yoo, T. W. Kim, S. Kim, J. Chang, and E. Y. Choi. 2009. Cognate CD4 help is essential for the reactivation and expansion of CD8 memory T cells directed against the hematopoietic cell-specific dominant minor histocompatibility antigen, H60. Blood 113: 4273-4280. https://doi.org/10.1182/blood-2008-09-181263
  5. Bennett, S. R., F. R. Carbone, F. Karamalis, R. A. Flavell, J. F. Miller, and W. R. Heath. 1998. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 393: 478-480. https://doi.org/10.1038/30996
  6. Schoenberger, S. P., R. E. Toes, E. I. van der Voort, R. Offringa, and C. J. Melief. 1998. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393: 480-483. https://doi.org/10.1038/31002
  7. Ridge, J. P., F. Di Rosa, and P. Matzinger. 1998. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 393: 474-478. https://doi.org/10.1038/30989
  8. Jung, K. M., and E. Y. Choi. 2007. Role for CD40 and CD40L Expression in Generating CD8 T Cell Response to Minor Histcompatibility Antigen, H60. Immune. Netw. 7: 173-178. https://doi.org/10.4110/in.2007.7.4.173
  9. Rahemtulla, A., W. P. Fung-Leung, M. W. Schilham, T. M. Kündig, S. R. Sambhara, A. Narendran, A. Arabian, A. Wakeham, C. J. Paige, R. M. Zinkernagel, and R. G. Miller & T. 1991. Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature 353: 180-184. https://doi.org/10.1038/353180a0
  10. Bevan, M. J. 2004. Helping the CD8(+) T-cell response. Nat. Rev. Immunol. 4: 595-602. https://doi.org/10.1038/nri1413
  11. Janssen, E. M., E. E. Lemmens, T. Wolfe, U. Christen, M. G. von Herrath, and S. P. Schoenberger. 2003. CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Nature 421: 852-856. https://doi.org/10.1038/nature01441
  12. Shedlock, D. J., and H. Shen. 2003. Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science 300: 337-339. https://doi.org/10.1126/science.1082305
  13. Sun, J. C., and M. J. Bevan. 2003. Defective CD8 T cell memory following acute infection without CD4 T cell help. Science 300: 339-342. https://doi.org/10.1126/science.1083317
  14. Roopenian, D., E. Y. Choi, and A. Brown. 2002. The immunogenomics of minor histocompatibility antigens. Immunol. Rev. 190: 86-94. https://doi.org/10.1034/j.1600-065X.2002.19007.x
  15. Choi, E. Y., Y. Yoshimura, G. J. Christianson, T. J. Sproule, S. Malarkannan, N. Shastri, S. Joyce, and D. C. Roopenian. 2001. Quantitative analysis of the immune response to mouse non-MHC transplantation antigens in vivo: the H60 histocompatibility antigen dominates over all others. J. Immunol. 166: 4370-4379. https://doi.org/10.4049/jimmunol.166.7.4370
  16. Choi, E. Y., G. J. Christianson, Y. Yoshimura, T. J. Sproule, N. Jung, S. Joyce, and D. C. Roopenian. 2002. Immunodominance of H60 is caused by an abnormally high precursor T cell pool directed against its unique minor histocompatibility antigen peptide. Immunity. 17: 593-603. https://doi.org/10.1016/S1074-7613(02)00428-4
  17. Malarkannan, S., P. P. Shih, P. A. Eden, T. Horng, A. R. Zuberi, G. Christianson, D. Roopenian, and N. Shastri. 1998. The molecular and functional characterization of a dominant minor H antigen, H60. J. Immunol. 161: 3501-3509.
  18. Warren, E. H., N. Fujii, Y. Akatsuka, C. N. Chaney, J. K. Mito, K. R. Loeb, T. A. Gooley, M. L. Brown, K. K. Koo, K. V. Rosinski, S. Ogawa, A. Matsubara, F. R. Appelbaum, and S. R. Riddell. 2010. Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens. Blood 115: 3869- 3878. https://doi.org/10.1182/blood-2009-10-248997
  19. Choi, J. H., S. J. Ryu, K. M. Jung, S. Kim, J. Chang, T. W. Kim, and E. Y. Choi. 2009. TCR diversity of H60-specific CD8 T cells during the response evolution and influence of CD4 help. Transplantation 87: 1609-1616. https://doi.org/10.1097/TP.0b013e3181a52dc4
  20. Harrington, L. E., R. Most Rv, J. L. Whitton, and R. Ahmed. 2002. Recombinant vaccinia virus-induced T-cell immunity: quantitation of the response to the virus vector and the foreign epitope. J. Virol. 76: 3329-3337. https://doi.org/10.1128/JVI.76.7.3329-3337.2002
  21. Xu, R., A. J. Johnson, D. Liggitt, and M. J. Bevan. 2004. Cellular and humoral immunity against vaccinia virus infection of mice. J. Immunol. 172: 6265-6271. https://doi.org/10.4049/jimmunol.172.10.6265
  22. Norbury, C. C., M. F. Princiotta, I. Bacik, R. R. Brutkiewicz, P. Wood, T. Elliott, J. R. Bennink, and J. W. Yewdell. 2001. Multiple antigen-specific processing pathways for activating naive CD8+ T cells in vivo. J. Immunol. 166: 4355-4362. https://doi.org/10.4049/jimmunol.166.7.4355
  23. Novy, P., M. Quigley, X. Huang, and Y. Yang. 2007. CD4 T cells are required for CD8 T cell survival during both pri mary and memory recall responses. J. Immunol. 179: 8243- 8251. https://doi.org/10.4049/jimmunol.179.12.8243
  24. Agnellini, P., M. Wiesel, K. Schwarz, P. Wolint, M. F. Bachmann, and A. Oxenius. 2008. Kinetic and mechanistic requirements for helping CD8 T cells. J. Immunol. 180: 1517-1525. https://doi.org/10.4049/jimmunol.180.3.1517
  25. Bacik, I., J. H. Cox, R. Anderson, J. W. Yewdell, and J. R. Bennink. 1994. TAP (transporter associated with antigen processing)-independent presentation of endogenously synthesized peptides is enhanced by endoplasmic reticulum insertion sequences located at the amino- but not carboxyl-terminus of the peptide. J. Immunol. 152: 381-387.
  26. Hwang, M. L., J. R. Lukens, and T. N. Bullock. 2007. Cognate memory CD4+ T cells generated with dendritic cell priming influence the expansion, trafficking, and differentiation of secondary CD8+ T cells and enhance tumor control. J. Immunol. 179: 5829-5838. https://doi.org/10.4049/jimmunol.179.9.5829
  27. Xiao, Z., J. M. Curtsinger, M. Prlic, S. C. Jameson, and M. F. Mescher. 2007. The CD8 T cell response to vaccinia virus exhibits site-dependent heterogeneity of functional responses. Int. Immunol. 19: 733-743. https://doi.org/10.1093/intimm/dxm039
  28. Moutaftsi, M., H. H. Bui, B. Peters, J. Sidney, S. Salek- Ardakani, C. Oseroff, V. Pasquetto, S. M. Crotty, Croft, E. J. Lefkowitz, H. Grey, and A. Sette. 2007. Vaccinia virus-specific CD4+ T cell responses target a set of antigens largely distinct from those targeted by CD8+ T cell responses. J. Immunol. 178: 6814-6820. https://doi.org/10.4049/jimmunol.178.11.6814
  29. Yang, Y., Z. Xiang, H. C. Ertl, and J. M. Wilson. 1995. Upregulation of class I major histocompatibility complex antigens by interferon gamma is necessary for T-cell-mediated elimination of recombinant adenovirus-infected hepatocytes in vivo. Proc. Natl. Acad. Sci. U. S. A. 92: 7257-7261. https://doi.org/10.1073/pnas.92.16.7257
  30. Van Deusen, K. E., R. Rajapakse, and T. N. Bullock. 2010. CD70 expression by dendritic cells plays a critical role in the immunogenicity of CD40-independent, CD4+ T cell-dependent, licensed CD8+ T cell responses. J. Leukoc. Biol. 87: 477-485. https://doi.org/10.1189/jlb.0809535