1887

Abstract

CD8 T lymphocytes play a major role in the clearance of respiratory syncytial virus (RSV) infections. To be able to study the primary CTL response in RSV-infected children, epitopes presented by a set of commonly used HLA alleles (HLA-A1, -A3, -B44 and -B51) were searched for. Five epitopes were characterized derived from the matrix (M), non-structural (NS2) and second matrix (M2) proteins of RSV. All epitopes were shown to be processed and presented by RSV-infected antigen-presenting cells. HLA-A1 tetramers for one of these epitopes derived from the M protein were constructed and used to quantify and phenotype the memory CD8 T cell pool in a panel of healthy adult donors. In about 60 % of the donors, CD8 T cells specific for the M protein could be identified. These cells belonged to the memory T cell subset characterized by expression of CD27 and CD28, and down-regulation of CCR7 and CD45RA. The frequency of tetramer-positive cells varied between 0·4 and 3 per 10 CD8 T cells in PBMC of healthy asymptomatic adult donors.

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2004-08-01
2019-11-21
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References

  1. Alwan, W. H., Record, F. M. & Openshaw, P. J. ( 1992; ). CD4+ T cells clear virus but augment disease in mice infected with respiratory syncytial virus. Comparison with the effects of CD8+ T cells. Clin Exp Immunol 88, 527–536.
    [Google Scholar]
  2. Alwan, W. H., Kozlowska, W. J. & Openshaw, P. J. ( 1994; ). Distinct types of lung disease caused by functional subsets of antiviral T cells. J Exp Med 179, 81–89.[CrossRef]
    [Google Scholar]
  3. Appay, V., Dunbar, P. R., Callan, M. & 18 other authors ( 2002; ). Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med 8, 379–385.[CrossRef]
    [Google Scholar]
  4. Bont, L., Heijnen, C. J., Kavelaars, A., van Aalderen, W. M., Brus, F., Draaisma, J. T., Geelen, S. M., van Vught, H. J. & Kimpen, J. L. ( 1999; ). Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis. Eur Respir J 14, 144–149.[CrossRef]
    [Google Scholar]
  5. Brandenburg, A. H., de Waal, L., Timmerman, H. H., Hoogerhout, P., de Swart, R. L. & Osterhaus, A. D. ( 2000; ). HLA class I-restricted cytotoxic T-cell epitopes of the respiratory syncytial virus fusion protein. J Virol 74, 10240–10244.[CrossRef]
    [Google Scholar]
  6. Brandt, C. D., Kim, H. W., Arrobio, J. O., Jeffries, B. C., Wood, S. C., Chanock, R. M. & Parrott, R. H. ( 1973; ). Epidemiology of respiratory syncytial virus infection in Washington, DC. Composite analysis of eleven consecutive yearly epidemics. Am J Epidemiol 98, 355–364.
    [Google Scholar]
  7. 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. J Exp Med 187, 1395–1402.[CrossRef]
    [Google Scholar]
  8. Cannon, M. J., Stott, E. J., Taylor, G. & Askonas, B. A. ( 1987; ). Clearance of persistent respiratory syncytial virus infections in immunodeficient mice following transfer of primed T cells. Immunology 62, 133–138.
    [Google Scholar]
  9. Cannon, M. J., Openshaw, P. J. & Askonas, B. A. ( 1988; ). Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus. J Exp Med 168, 1163–1168.[CrossRef]
    [Google Scholar]
  10. Cherrie, A. H., Anderson, K., Wertz, G. W. & Openshaw, P. J. ( 1992; ). Human cytotoxic T cells stimulated by antigen on dendritic cells recognize the N, SH, F, M, 22K, and 1b proteins of respiratory syncytial virus. J Virol 66, 2102–2110.
    [Google Scholar]
  11. de Waal, L., Koopman, L. P., van Benten, I. J., Brandenburg, A. H., Mulder, P. G., de Swart, R. L., Fokkens, W. J., Neijens, H. J. & Osterhaus, A. D. ( 2003; ). Moderate local and systemic respiratory syncytial virus-specific T-cell responses upon mild or subclinical RSV infection. J Med Virol 70, 309–318.[CrossRef]
    [Google Scholar]
  12. Goulder, P. J., Lechner, F., Klenerman, P., McIntosh, K. & Walker, B. D. ( 2000; ). Characterization of a novel respiratory syncytial virus-specific human cytotoxic T-lymphocyte epitope. J Virol 74, 7694–7697.[CrossRef]
    [Google Scholar]
  13. Graham, B. S., Bunton, L. A., Wright, P. F. & Karzon, D. T. ( 1991; ). Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice. J Clin Invest 88, 1026–1033.[CrossRef]
    [Google Scholar]
  14. Hall, C. B., Powell, K. R., MacDonald, N. E., Gala, C. L., Menegus, M. E., Suffin, S. C. & Cohen, H. J. ( 1986; ). Respiratory syncytial viral infection in children with compromised immune function. N Engl J Med 315, 77–81.[CrossRef]
    [Google Scholar]
  15. He, X. S., Mahmood, K., Maecker, H. T., Holmes, T. H., Kemble, G. W., Arvin, A. M. & Greenberg, H. B. ( 2003; ). Analysis of the frequencies and of the memory T cell phenotypes of human CD8+ T cells specific for influenza A viruses. J Infect Dis 187, 1075–1084.[CrossRef]
    [Google Scholar]
  16. Hislop, A. D., Gudgeon, N. H., Callan, M. F., Fazou, C., Hasegawa, H., Salmon, M. & Rickinson, A. B. ( 2001; ). EBV-specific CD8+ T cell memory: relationships between epitope specificity, cell phenotype, and immediate effector function. J Immunol 167, 2019–2029.[CrossRef]
    [Google Scholar]
  17. Isaacs, D., Bangham, C. R. & McMichael, A. J. ( 1987; ). Cell-mediated cytotoxic response to respiratory syncytial virus in infants with bronchiolitis. Lancet ii, 769–771.
    [Google Scholar]
  18. Mbawuike, I. N., Wells, J., Byrd, R., Cron, S. G., Glezen, W. P. & Piedra, P. A. ( 2001; ). HLA-restricted CD8+ cytotoxic T lymphocyte, interferon-γ, and interleukin-4 responses to respiratory syncytial virus infection in infants and children. J Infect Dis 183, 687–696.[CrossRef]
    [Google Scholar]
  19. Rammensee, H., Bachmann, J., Emmerich, N. P., Bachor, O. A. & Stevanovic, S. ( 1999; ). syfpeithi: database for MHC ligands and peptide motifs. Immunogenetics 50, 213–219.[CrossRef]
    [Google Scholar]
  20. Rock, M. T. & Crowe, J. E. ( 2003; ). Identification of a novel human leucocyte antigen-A*01-restricted cytotoxic T-lymphocyte epitope in the respiratory syncytial virus fusion protein. Immunology 108, 474–480.[CrossRef]
    [Google Scholar]
  21. Salkind, A. R., McCarthy, D. O., Nichols, J. E., Domurat, F. M., Walsh, E. E. & Roberts, N. J., Jr ( 1991; ). Interleukin-1-inhibitor activity induced by respiratory syncytial virus: abrogation of virus-specific and alternate human lymphocyte proliferative responses. J Infect Dis 163, 71–77.[CrossRef]
    [Google Scholar]
  22. Schlender, J., Walliser, G., Fricke, J. & Conzelmann, K. K. ( 2002; ). Respiratory syncytial virus fusion protein mediates inhibition of mitogen-induced T-cell proliferation by contact. J Virol 76, 1163–1170.[CrossRef]
    [Google Scholar]
  23. Shay, D. K., Holman, R. C., Newman, R. D., Liu, L. L., Stout, J. W. & Anderson, L. J. ( 1999; ). Bronchiolitis-associated hospitalizations among US children, 1980–1996. JAMA 282, 1440–1446.[CrossRef]
    [Google Scholar]
  24. Sigurs, N., Bjarnason, R., Sigurbergsson, F. & Kjellman, B. ( 2000; ). Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med 161, 1501–1507.[CrossRef]
    [Google Scholar]
  25. Stein, R. T., Sherrill, D., Morgan, W. J., Holberg, C. J., Halonen, M., Taussig, L. M., Wright, A. L. & Martinez, F. D. ( 1999; ). Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 354, 541–545.[CrossRef]
    [Google Scholar]
  26. Urbani, S., Boni, C., Missale, G., Elia, G., Cavallo, C., Massari, M., Raimondo, G. & Ferrari, C. ( 2002; ). Virus-specific CD8+ lymphocytes share the same effector-memory phenotype but exhibit functional differences in acute hepatitis B and C. J Virol 76, 12423–12434.[CrossRef]
    [Google Scholar]
  27. van Lier, R. A., ten Berge, I. J. & Gamadia, L. E. ( 2003; ). Human CD8+ T-cell differentiation in response to viruses. Nat Rev Immunol 3, 931–939.[CrossRef]
    [Google Scholar]
  28. Venter, M., Rock, M., Puren, A. J., Tiemessen, C. T. & Crowe, J. E., Jr ( 2003; ). Respiratory syncytial virus nucleoprotein-specific cytotoxic T-cell epitopes in a South African population of diverse HLA types are conserved in circulating field strains. J Virol 77, 7319–7329.[CrossRef]
    [Google Scholar]
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