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Volume 81, Issue 5

A novel sensitive approach for frequency analysis of measles virus-specific memory T-lymphocytes in healthy adults with a childhood history of natural measles Free

Abstract

Measles virus (MV), a single-stranded negative-sense RNA virus, is an important pathogen causing almost 1 million deaths annually. Acute MV infection induces immunity against disease throughout life. The immunological factors which are responsible for protection against measles are still poorly understood. However, T-cell-mediated immune responses seem to play a central role. The emergence of new single-cell methods for quantification of antigen-specific T-cells directly has prompted us to measure frequencies of MV-specific memory T-cells. As an indicator for T-cell activation IFN-γ production was measured. PBMC were analysed by intracellular staining and ELISPOT assay after stimulation with MV-infected autologous B-lymphoblastoid cell lines or dendritic cells. T-cell responses were exclusively seen with PBMC from MV-seropositive healthy adults with a history of natural measles in childhood. The median frequency of MV-specific T-cells was 0·35% for CD3CD4 and 0·24% for the CD3CD8 T-cell subset. These frequencies are comparable with T-cell numbers reported by other investigators for persistent virus infections such as Epstein–Barr virus, cytomegalovirus or human immunodeficiency virus. Hence, this study illustrates that MV-specific CD4 and CD8 T-cells are readily detectable long after the acute infection, and thus are probably contributing to long-term immunity. Furthermore, this new approach allows efficient analysis of T-cell responses from small samples of blood and could therefore be a useful tool to further elucidate the role of cell-mediated immunity in measles as well as in other viral infections.

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© Microbiology Society
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2000-05-01
2024-04-24
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References

  1. Altman, J. D., Moss, P. A. H., Goulder, P. J. R., Barouch, D. H., McHeyzer-Williams, M. G., Bell, J. I., McMichael, A. J. & Davis, M. M. (1996). Phenotypic analysis of antigen-specific T lymphocytes.Science 274, 94-96.[CrossRef] [Google Scholar]
  2. Burnet, F. M. (1968). Measles as an index for immunological function.Lancet ii, 610-663. [Google Scholar]
  3. Busch, D. H., Pilip, I. M., Vijh, S. & Pamer, E. G. (1998). Coordinate regulation of complex T-cell populations responding to bacterial infection.Immunity 8, 353-362.[CrossRef] [Google Scholar]
  4. Butz, E. A. & Bevan, M. J. (1998). Massive expansion of antigen-specific CD8+ T-cells during an acute virus infection.Immunity 8, 167-175.[CrossRef] [Google Scholar]
  5. Callan, M. F., Tan, L., Annels, N., Ogg, G. S., Wilson, J. D., O’Callaghan, C. A., Steven, N., McMichael, A. J. & Rickinson, A. B. (1998). Direct visualization of antigen-specific CD8+ T-cells during the primary immune response to Epstein-Barr virus in vivo.Journal of Experimental Medicine 187, 1395-1402.[CrossRef] [Google Scholar]
  6. Chen, R. T., Markowitz, L. E., Albrecht, P., Stewart, J. A., Mofenson, L. M., Preblud, S. R. & Orenstein, W. A. (1990). Measles antibody: reevaluation of protective titers.Journal of Infectious Diseases 162, 1036-1042.[CrossRef] [Google Scholar]
  7. Crawford, F., Kozono, H., White, J., Marrack, P. & Kappler, J. (1998). Detection of antigen-specific T-cells with multivalent soluble class II MHC covalent peptide complexes.Immunity 8, 675-682.[CrossRef] [Google Scholar]
  8. Dalod, M., Sinet, M., Deschemin, J. C., Fiorentino, S., Venet, A. & Guillet, J. G. (1999a). Altered ex vivo balance between CD28+ and CD28− cells within HIV-specific CD8+ T-cells of HIV-seropositive patients.European Journal of Immunology 29, 38-44.[CrossRef] [Google Scholar]
  9. Dalod, M., Dupuis, M., Deschemin, J. C., Sicard, D., Salmon, D., Delfraissy, J. F., Venet, A., Sinet, M. & Guillet, J. G. (1999b). Broad intense anti-human immunodeficiency virus (HIV) ex vivo CD8+ responses in HIV type 1-infected patients: comparison with anti-Epstein-Barr virus responses and changes during antiretroviral therapy.Journal of Virology 73, 7108-7116. [Google Scholar]
  10. Doherty, P. C. (1998). The numbers game for virus-specific CD8+ T-cells.Science 280, 227.[CrossRef] [Google Scholar]
  11. Engelking, O., Fedorov, L. M., Lilischkis, R., ter Meulen, V. & Schneider-Schaulies, S. (1999). Measles virus-induced immunosuppression in vitro is associated with deregulation of G1 cell cycle control proteins.Journal of General Virology 80, 1599-1608. [Google Scholar]
  12. Esolen, L. M., Ward, B. J., Moench, T. R. & Griffin, D. E. (1993). Infection of monocytes during measles.Journal of Infectious Diseases 168, 47-52.[CrossRef] [Google Scholar]
  13. Flynn, K. J., Belz, G. T., Altman, J. D., Ahmed, R., Woodland, D. L. & Doherty, P. C. (1998). Virus-specific CD8+ T-cells in primary and secondary influenza pneumonia.Immunity 8, 683-691.[CrossRef] [Google Scholar]
  14. Fujihashi, K., McGhee, J. R., Beagley, K. W., McPherson, D. T., McPherson, S. A., Huang, C. M. & Kiyono, H. (1993). Cytokine-specific ELISPOT assay. Single cell analysis of IL-2, IL-4 and IL-6 producing cells.Journal of Immunological Methods 160, 181-189.[CrossRef] [Google Scholar]
  15. Gustafson, T. L., Lievens, A. W., Brunell, P. A., Moellenberg, R. G., Buttery, C. M. & Sehulster, L. M. (1987). Measles outbreak in a fully immunized secondary-school population.New England Journal of Medicine 316, 771-774.[CrossRef] [Google Scholar]
  16. Jacobson, S., Richert, J. R., Biddison, W. E., Satinsky, A., Hartzman, R. J. & McFarland, H. F. (1984). Measles virus-specific T4+ human cytotoxic T-cell clones are restricted by class II HLA antigens.Journal of Immunology 133, 754-757. [Google Scholar]
  17. Joseph, B. S., Lampert, P. W. & Oldstone, M. B. (1975). Replication and persistence of measles virus in defined subpopulations of human leukocytes.Journal of Virology 16, 1638-1649. [Google Scholar]
  18. Kalams, S. A. & Walker, B. D. (1998). The critical need for CD4 help in maintaining effective cytotoxic T lymphocyte responses.Journal of Experimental Medicine 188, 2199-2204.[CrossRef] [Google Scholar]
  19. Katz, M. (1995). Clinical spectrum of measles.Current Topics in Microbiology and Immunology 191, 1-12. [Google Scholar]
  20. Kern, F., Surel, I. P., Brock, C., Freistedt, B., Radtke, H., Scheffold, A., Blasczyk, R., Reinke, P., Schneider-Mergener, J., Radbruch, A., Walden, P. & Volk, H. D. (1998). T-cell epitope mapping by flow cytometry.Nature Medicine 4, 975-978.[CrossRef] [Google Scholar]
  21. McChesney, M. B. & Oldstone, M. B. (1989). Virus-induced immunosuppression: infections with measles virus and human immunodeficiency virus.Advanced Immunology 45, 335-380. [Google Scholar]
  22. Mongkolsapaya, J., Jaye, A., Callan, M. F. C., Magnusen, A. F., McMichael, A. J. & Whittle, H. C. (1999). Antigen-specific expansion of cytotoxic T lymphocytes in acute measles virus infection.Journal of Virology 73, 67-71. [Google Scholar]
  23. Murali-Krishna, K., Altman, J. D., Suresh, M., Sourdive, D. J., Zajac, A. J., Miller, J. D., Slansky, J. & Ahmed, R. (1998). Counting antigen-specific CD8 T-cells: a re-evaluation of bystander activation during viral infection.Immunity 8, 177-187.[CrossRef] [Google Scholar]
  24. Nanan, R., Carstens, C. & Kreth, H. W. (1995). Demonstration of virus-specific CD8+ memory T-cells in measles-seropositive individuals by in vitro peptide stimulation.Clinical and Experimental Immunology 102, 40-45. [Google Scholar]
  25. Openshaw, P., Murphy, E. E., Hosken, N. A., Maino, V., Davis, K., Murphy, K. & O’Garra, A. (1995). Heterogeneity of intracellular cytokine synthesis at the single-cell level in polarized T helper 1 and T helper 2 populations.Journal of Experimental Medicine 182, 1357-1367.[CrossRef] [Google Scholar]
  26. Panum, P. L. (1940).Observation made during the epidemics of measles in the Faroe Islands in the year 1846. New York: New York Public Health Association.
  27. Pitcher, C. J., Quittner, C., Peterson, D. M., Connors, M., Koup, R. A., Maino, V. C. & Picker, L. J. (1999). HIV-1-specific CD4+ T-cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression. Nature Medicine 518–525. [Google Scholar]
  28. Richardson, C. D. & Choppin, P. W. (1983). Oligopeptides that specifically inhibit membrane fusion by paramyxoviruses: studies on the site of action.Virology 131, 518-532.[CrossRef] [Google Scholar]
  29. Salter, R. D. & Cresswell, P. (1986). Impaired assembly and transport of HLA-A and -B antigens in a mutant T×B cell hybrid.EMBO Journal 5, 943-949. [Google Scholar]
  30. Sarawar, S. R. & Doherty, P. C. (1994). Concurrent production of interleukin-2, interleukin-10, and gamma interferon in the regional lymph nodes of mice with influenza pneumonia.Journal of Virology 68, 3112-3119. [Google Scholar]
  31. Scheibenbogen, C., Lee, K. H., Stevanovic, S., Witzens, M., Willhauck, M., Waldmann, V., Naeher, H., Rammensee, H. G. & Keilholz, U. (1997). Analysis of the T-cell response to tumor and viral peptide antigens by an IFNgamma-ELISPOT assay.International Journal of Cancer 71, 932-936.[CrossRef] [Google Scholar]
  32. Tan, L. C., Gudgeon, N., Annels, N. E., Hansasuta, P., O’Callaghan, C. A., Rowland-Jones, S., McMichael, A. J., Rickinson, A. B. & Callan, M. F. (1999). A re-evaluation of the frequency of CD8+ T-cells specific for EBV in healthy virus carriers.Journal of Immunology 162, 1827-1835. [Google Scholar]
  33. Thiele, D. L. & Lipsky, P. E. (1985). Modulation of human natural killer cell function by l-leucine methylester: monocyte-dependent depletion from human peripheral blood mononuclear cells.Journal of Immunology 134, 786-790. [Google Scholar]
  34. Van Binnendijk, R. S., Poelen, M. C., Kuijpers, K. C., Osterhaus, A. D. & Uytdehaag, F. G. (1990). The predominance of CD8+ T-cells after infection with measles virus suggests a role for CD8+ class I MHC-restricted cytotoxic T lymphocytes (CTL) in recovery from measles. Clonal analyses of human CD8+ class I MHC-restricted CTL.Journal of Immunology 144, 2394-2399. [Google Scholar]
  35. Waldrop, S. L., Pitcher, C. J., Peterson, D. M., Maino, V. C. & Picker, L. J. (1997). Determination of antigen-specific memory/effector CD4+ T-cell frequencies by flow cytometry: evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency.Journal of Clinical Investigation 99, 1739-1750.[CrossRef] [Google Scholar]
  36. Zajac, A. J., Blattman, J. N., Murali-Krishna, K., Sourdive, D. J. D., Altman, J. D. & Ahmed, R. (1998). Viral immune evasion due to persistence of activated T cells without effector function.Journal of Experimental Medicine 188, 2205-2213.[CrossRef] [Google Scholar]
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A novel sensitive approach for frequency analysis of measles virus-specific memory T-lymphocytes in healthy adults with a childhood history of natural measles
J. Gen. Virol. 81, 1313 (2000); https://doi.org/10.1099/0022-1317-81-5-1313
/content/journal/jgv/10.1099/0022-1317-81-5-1313
/content/journal/jgv/10.1099/0022-1317-81-5-1313
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