Journal of Microbiology and Biotechnology

  • 제17권12호
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  • Pages.1955-1964
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  • 2007
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  • 1017-7825(pISSN)
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  • 1738-8872(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
권호 표지

Intracellular CD154 Expression Reflects Antigen-specific $CD8^+\;T$ Cells but Shows Less Sensitivity than Intracellular Cytokine and MHC Tetramer Staining

  • Han, Young-Woo (Department of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University) ;
  • Aleyas, Abi G. (Department of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University) ;
  • George, Junu A. (Department of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University) ;
  • Yoon, Hyun-A (Department of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University) ;
  • Lee, John-Hwa (Department of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University) ;
  • Kim, Byung-Sam (Immunomodulation Research Center, University of Ulsan) ;
  • Eo, Seong-Kug (Department of Microbiology, College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University)
  • 발행 : 2007.12.31
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초록

A recent report showed that analysis of CD154 expression in the presence of the secretion inhibitor Brefeldin A (Bref A) could be used to assess the entire repertoire of antigen-specific $CD4^+\;T$ helper cells. However, the capacity of intracellular CD154 expression to identify antigen-specific $CD8^+\;T$ cells has yet to be investigated. In this study, we compared the ability of intracellular CD154 expression to assess antigen-specific $CD8^+\;T$ cells with that of accepted standard assays, namely intracellular cytokine IFN-${\gamma}$ staining (ICS) and MHC class I tetramer staining. The detection of intracellular CD154 molecules in the presence of Bref A reflected the kinetic trend of antigen-specific $CD8^+\;T$ cell number, but unfortunately showed less sensitivity than ICS and tetramer staining. However, ICS levels peaked and saturated 8 h after antigenic stimulation in the presence of Bref A and then declined, whereas intracellular CD154 expression peaked by 8 h and maintained the saturated level up to 24 h post-stimulation. Moreover, intracellular CD154 expression in antigen-specific $CD8^+\;T$ cells developed in the absence of $CD4^+\;T$ cells changed little, whereas the number of IFN-${\gamma}$-producing $CD8^+\;T$ cells decreased abruptly. These results suggest that intracellular CD154 could aid the assessment of antigen-specific $CD8^+\;T$ cells, but does not have as much ability to identify heterogeneous $CD4^+\;T$ helper cells. Therefore, the combined analytical techniques of ICS and tetramer staining together with intracellular CD154 assays may be able to provide useful information on the accurate phenotype and functionality of antigen-specific $CD8^+\;T$ cells.

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참고문헌

  1. Altman, J. D., P. A. Moss, P. J. Goulder, D. H. Barouch, M. G. McHeyzer-Williams, J. I. Bell, A. J. McMichael, and M. M. Davis. 1996. Phenotypic analysis of antigen-specific T lymphocytes. Science 274: 94-96 https://doi.org/10.1126/science.274.5284.94
  2. Appay, V., D. F. Nixon, S. M. Donahoe, G. M. Gillespie, T. Dong, A. King, G. S. Ogg, H. M. Spiegel, C. Conlon, C. A. Spina, D. V. Havlir, D. D. Richman, A. Waters, P. Easterbrook, A. J. McMichael, and S. L. Rowland-Jones. 2000. HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function. J. Exp. Med. 192: 63-75 https://doi.org/10.1084/jem.192.1.63
  3. Armitage, R. J., W. C. Fanslow, L. Strockbine, T. A. Sato, K. N. Clifford, B. M. Macduff, D. M. Anderson, S. D. Gimpel, T. Davis-Smith, C. R. Maliszewski, et al. 1992. Molecular and biological characterization of a murine ligand for CD40. Nature 357: 80-82 https://doi.org/10.1038/357080a0
  4. Barber, D. L., E. J. Wherry, D. Masopust, B. Zhu, J. P. Allison, A. H. Sharpe, G. J. Freeman, and R. Ahmed. 2006. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439: 682-687 https://doi.org/10.1038/nature04444
  5. Bartholomae, W. C., F. H. Rininsland, J. C. Eisenberg, B. O. Boehm, P. V. Lehmann, and M. Tary-Lehmann. 2004. T cell immunity induced by live, necrotic, and apoptotic tumor cells. J. Immunol. 173: 1012-1022 https://doi.org/10.4049/jimmunol.173.2.1012
  6. Beadling, C. and M. K. Slifka. 2006. Quantifying viable virus-specific T cells without a priori knowledge of fine epitope specificity. Nat. Med. 12: 1208-1212 https://doi.org/10.1038/nm1413
  7. Behrens, G., M. Li, C. M. Smith, G. T. Belz, J. Mintern, F. R. Carbone, and W. R. Heath. 2004. Helper T cells, dendritic cells and CTL immunity. Immunol. Cell Biol. 82: 84-90 https://doi.org/10.1111/j.1440-1711.2004.01211.x
  8. Betts, M. R., J. M. Brenchley, D. A. Price, S. C. De Rosa, D. C. Douek, M. Roederer, and R. A. Koup. 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
  9. Betts, M. R., J. P. Casazza, B. A. Patterson, S. Waldrop, W. Trigona, T. M. Fu, F. Kern, L. J. Picker, and R. A. Koup. 2000. Putative immunodominant human immunodeficiency virus-specific CD8(+) T-cell responses cannot be predicted by major histocompatibility complex class I haplotype. J. Virol. 74: 9144-9151 https://doi.org/10.1128/JVI.74.19.9144-9151.2000
  10. Chang, J., J. H. Cho, S. W. Lee, S. Y. Choi, S. J. Ha, and Y. C. Sung. 2004. IL-12 priming during in vitro antigenic stimulation changes properties of CD8 T cells and increases generation of effector and memory cells. J. Immunol. 172: 2818-2826 https://doi.org/10.4049/jimmunol.172.5.2818
  11. Chattopadhyay, P. K., J. Yu, and M. Roederer. 2005. Alivecell assay to detect antigen-specific CD4+ T cells with diverse cytokine profiles. Nat. Med. 11: 1113-1137 https://doi.org/10.1038/nm1293
  12. Clay, T. M., A. C. Hobeika, P. J. Mosca, H. K. Lyerly, and M. A. Morse. 2001. Assays for monitoring cellular immune responses to active immunotherapy of cancer. Clin. Cancer Res. 7: 1127-1135
  13. Douek, D. C., M. R. Betts, J. M. Brenchley, B. J. Hill, D. R. Ambrozak, K. L. Ngai, N. J. Karandikar, J. P. Casazza, and R. A. Koup. 2002. A novel approach to the analysis of specificity, clonality, and frequency of HIV-specific T cell responses reveals a potential mechanism for control of viral escape. J. Immunol. 168: 3099-3104 https://doi.org/10.4049/jimmunol.168.6.3099
  14. Fadel, S. A., L. G. Cowell, S. Cao, D. A. Ozaki, T. B. Kepler, D. A. Steeber, and M. Sarzotti. 2006. Neonate-primed CD8+ memory cells rival adult-primed memory cells in antigen-driven expansion and anti-viral protection. Int. Immunol. 18: 249-257 https://doi.org/10.1093/intimm/dxh360
  15. Falco, D. A., R. R. Nepomuceno, S. M. Krams, P. P. Lee, M. M. Davis, O. Salvatierra, S. R. Alexander, C. O. Esquivel, K. L. Cox, L. R. Frankel, and O. M. Martinez. 2002. Identification of Epstein-Barr virus-specific CD8+ T lymphocytes in the circulation of pediatric transplant recipients. Transplantation 74: 501-510 https://doi.org/10.1097/00007890-200208270-00012
  16. Frentsch, M., O. Arbach, D. Kirchhoff, B. Moewes, M. Worm, M. Rothe, A. Scheffold, and A. Thiel. 2005. Direct access to CD4+ T cells specific for defined antigens according to CD154 expression. Nat. Med. 11: 1118-1124 https://doi.org/10.1038/nm1292
  17. Graf, D., U. Korthauer, H. W. Mages, G. Senger, and R. A. Kroczek. 1992. Cloning of TRAP, a ligand for CD40 on human T cells. Eur. J. Immunol. 22: 3191-3194 https://doi.org/10.1002/eji.1830221226
  18. Hermann, P., C. Van-Kooten, C. Gaillard, J. Banchereau, and D. Blanchard. 1995. CD40 ligand-positive CD8+ T cell clones allow B cell growth and differentiation. Eur. J. Immunol. 25: 2972-2977 https://doi.org/10.1002/eji.1830251039
  19. Huang, X. L., Z. Fan, C. Kalinyak, J. W. Mellors, and C. R. Rinaldo Jr. 2000. CD8(+) T-cell gamma interferon production specific for human immunodeficiency virus type 1 (HIV-1) in HIV-1-infected subjects. Clin. Diagn. Lab. Immunol. 7: 279-287
  20. Kang, K. Y., C. H. Choi, J. Y. Oh, H. Kim, G. R. Kweon, and J. C. Lee. 2005. Chloramphenicol arrests transition of cell cycle and induces apoptotic cell death in myelogenous leukemia cells. J. Microbiol. Biotechnol. 15: 913-918
  21. Kern, F., I. P. Surel, C. Brock, B. Freistedt, H. Radtke, A. Scheffold, R. Blasczyk, P. Reinke, J. Schneider-Mergener, A. Radbruch, P. Walden, and H. D. Volk. 1998. T-cell epitope mapping by flow cytometry. Nat. Med. 4: 975-978 https://doi.org/10.1038/nm0898-975
  22. Kim, H. P., M. R. Jin, I. Y. Kim, B. Y. Ahn, and S. M. Kang. 1999. Analysis of the major histocompatibility complex class I antigen presentation machinery in human lung cancer. J. Microbiol. Biotechnol. 9: 346-351
  23. Koo, J. H., W. J. Chae, J. M. Choi, H. W. Nam, T. Morio, Y. S. Kim, Y. S. Jang, K. Y. Choi, J. J. Yang, and S. K. Lee. 2006. Proteomic analysis of resting and activated human CD8+ T cells. J. Microbiol. Biotechnol. 16: 911-920
  24. Kuzushima, K., N. Hayashi, A. Kudoh, Y. Akatsuka, K. Tsujimura, Y. Morishima, and T. Tsurumi. 2003. Tetramerassisted identification and characterization of epitopes recognized by HLA A*2402-restricted Epstein-Barr virusspecific CD8+ T cells. Blood 101: 1460-1468 https://doi.org/10.1182/blood-2002-04-1240
  25. Misumi, Y., Y. Misumi, K. Miki, A. Takatsuki, G. Tamura, and Y. Ikehara. 1986. Novel blockade by Brefeldin A of intracellular transport of secretory proteins in cultured rat hepatocytes. J. Biol. Chem. 261: 11398-11403
  26. Murali-Krishna, K., J. D. Altman, M. Suresh, D. J. Sourdive, A. J. Zajac, J. D. Miller, J. Slansky, and R. Ahmed. 1998. Counting antigen-specific CD8 T cells: A reevaluation of bystander activation during viral infection. Immunity 8: 177-187 https://doi.org/10.1016/S1074-7613(00)80470-7
  27. Roy, M., T. Waldschmidt, A. Aruffo, J. A. Ledbetter, and R. J. Noelle. 1993. The regulation of the expression of gp39, the CD40 ligand, on normal and cloned CD4+ T cells. J. Immunol. 151: 2497-2510
  28. Sad, S., L. Krishnan, R. C. Bleackley, D. Kagi, H. Hengartner, and T. R. Mosmann. 1997. Cytotoxicity and weak CD40 ligand expression of CD8+ type 2 cytotoxic T cells restricts their potential B cell helper activity. Eur. J. Immunol. 27: 914-922 https://doi.org/10.1002/eji.1830270417
  29. Salem, M. L., A. N. Kadima, D. J. Cole, and W. E. Gillanders. 2005. Defining the antigen-specific T-cell response to vaccination and poly(I:C)/TLR3 signaling: Evidence of enhanced primary and memory CD8 T-cell responses and antitumor immunity. J. Immunother. 28: 220-228 https://doi.org/10.1097/01.cji.0000156828.75196.0d
  30. Scott-Algara, D., F. Buseyne, F. Porrot, B. Corre, N. Bellal, C. Rouzioux, S. Blanche, and Y. Riviere. 2005. Not all tetramer binding CD8+ T cells can produce cytokines and chemokines involved in the effector functions of virusspecific CD8+ T lymphocytes in HIV-1 infected children. J. Clin. Immunol. 25: 57-67 https://doi.org/10.1007/s10875-005-0358-3
  31. 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
  32. Sonn, C. H., H. R. Yoon, I. O. Seong, M. R. Chang, Y. C. Kim, H. C. Kang, S. C. Suh, and Y. S. Kim. 2006. MethA fibrosarcoma cells expressing membrane-bound forms of IL- 2 enhance antitumor immunity. J. Microbiol. Biotechnol. 16: 1919-1927
  33. 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
  34. Trapani, J. A. and M. J. Smyth. 2002. Functional significance of the perforin/granzyme cell death pathway. Nat. Rev. Immunol. 2: 735-747 https://doi.org/10.1038/nri911
  35. Trautmann, L., L. Janbazian, N. Chomont, E. A. Said, S. Gimmig, B. Bessette, M. R. Boulassel, E. Delwart, H. Sepulveda, R. S. Balderas, J. P. Routy, E. K. Haddad, and R. P. Sekaly. 2006. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat. Med. 12: 1198-1202 https://doi.org/10.1038/nm1482
  36. van Kooten, C. and J. Banchereau. 2000. CD40-CD40 ligand. J. Leukoc. Biol. 67: 2-17 https://doi.org/10.1002/jlb.67.1.2
  37. Walker, E. B. and M. L. Disis. 2003. Monitoring immune responses in cancer patients receiving tumor vaccines. Int. Rev. Immunol. 22: 283-319 https://doi.org/10.1080/08830180305226
  38. Whiteside, T. L. and J. A. Hank. 2002. Monitoring of immunologic therapies, pp. 1108-1117. In R. G. H. R. N. Rose, and B. Detrick (eds.), Manual of Clinical Laboratory Immunology, 6th Ed. ASM, Washington, DC
  39. Yellin, M. J., K. Sippel, G. Inghirami, L. R. Covey, J. J. Lee, J. Sinning, E. A. Clark, L. Chess, and S. Lederman. 1994. CD40 molecules induce down-modulation and endocytosis of T cell surface T cell-B cell activating molecule/CD40-L. Potential role in regulating helper effector function. J. Immunol. 152: 598-608
  40. Yim, S. B. and Y. H. Chung. 2004. Construction and production of concatameric human TNF receptor-immunoglobulin fusion proteins. J. Microbiol. Biotechnol. 14: 81-89