1887

Abstract

T-cell-mediated immune responses against mucosal oncogenic types of human papillomaviruses (HPV) are thought to play a role in the control of the virus infection and its associated cervical lesions. The production of interleukin-2 by T-helper (Th) cells in response to the C-terminal and N-terminal domains of the HPV-16 E2 protein was determined in 74 women with cytological evidence of premalignant cervical epithelial neoplasia who participated in a non-intervention follow-up (FU) study. Cross-sectional analysis at the end of FU showed that Th cell responses against the C-terminal domain were associated with evidence of previous or present HPV-16 infection as compared to patients with no evidence of any HPV infection (18·9% versus 0%, =0·039). Th cell responses against the N-terminal domain were not associated with evidence of HPV-16 infection. No association with disease outcome was observed with Th cell responses against either of the E2 protein domains. However, longitudinal analysis revealed that Th cell responses against the C-terminal domain frequently occur at the time of virus clearance. Whether these responses are responsible for the clearance of the virus is not known.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-80-9-2453
1999-09-01
2020-07-05
Loading full text...

Full text loading...

/deliver/fulltext/jgv/80/9/0802453a.html?itemId=/content/journal/jgv/10.1099/0022-1317-80-9-2453&mimeType=html&fmt=ahah

References

  1. Bouvard V., Storey A., Pim D., Banks L.. 1994; Characterization of the human papillomavirus E2 protein: evidence of trans-activation and trans-repression in cervical keratinocytes. EMBO Journal13:5451–5459
    [Google Scholar]
  2. Cripe T. P., Haugen T. H., Turk J. P., Schmid P. G., Durst M., Gissmann L., Roman A., Turek L. P.. 1987; Transcriptional regulation of the human papillomavirus type-16 E6–E7 promoter by a keratinocyte-dependent enhancer, and by viral E2 trans-activator and repressor gene products: implications for cervical carcinogenesis. EMBO Journal6:3745–3753
    [Google Scholar]
  3. Cullen A. P., Reid R., Campion M., Lorincz A. T.. 1991; Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm. Journal of Virology65:606–612
    [Google Scholar]
  4. de Gruijl T. D., Bontkes H. J., Walboomers J. M. M., Stukart M. J., Doekhie F. S., Remmink A. J., Helmerhorst T. J. M., Verheijen R. H. M., Duggan-Keen M. F., Stern P. L., Meijer C. J. L. M., Scheper R. J.. 1998; Differential T helper cell responses to human papillomavirus type 16 E7 related to viral clearance or persistence in patients with cervical neoplasia: a longitudinal study. Cancer Research58:1700–1706
    [Google Scholar]
  5. Demeret C., Yaniv M., Thierry F.. 1994; The E2 transcriptional repressor can compensate for Sp1 activation of the human papillomavirus type 18 early promoter. Journal of Virology68:7075–7082
    [Google Scholar]
  6. de Roda Husman A.-M., Walboomers J. M. M., Meijer C. J. L. M., Risse E. K. J., Schipper M. E. I., Helmerhorst T. J. M., Bleker O. P., Delius H., van den Brule A. J. C., Snijders P. J. F.. 1994; Analysis of cytomorphologically abnormal cervical scrapes for the presence of 27 mucosotropic human papillomavirus genotypes, using polymerase chain reaction. International Journal of Cancer56:802–806
    [Google Scholar]
  7. de Roda Husman A.-M., Walboomers J. M. M., van den Brule A. J. C., Meijer C. J. L. M., Snijders P. J. F.. 1995; The use of general primers GP5 and GP6 elongated at their 3′ ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. Journal of General Virology76:1057–1062
    [Google Scholar]
  8. Dillner J., Lenner P., Lehtinen M., Eklund C., Heino P., Wiklund F., Hallmans G., Stendahl U.. 1994; A population-based seroepidemiological study of cervical cancer. Cancer Research54:134–141
    [Google Scholar]
  9. Dillner J., Wiklund F., Lenner P., Eklund C., Frederiksson-Shanazarian V., Schiller J. T., Hibma M., Hallmans G., Stendahl U.. 1995; Antibodies against linear and conformational epitopes of human papillomavirus type 16 that independently associate with incident cervical cancer. International Journal of Cancer60:377–382
    [Google Scholar]
  10. Dowhanick J. J., McBride A. A., Howley P. M.. 1995; Suppression of cellular proliferation by the papillomavirus E2 protein. Journal of Virology69:7791–7799
    [Google Scholar]
  11. Ham J., Dostatni N., Gauthier J.-M., Yaniv M.. 1991; The papillomavirus E2 protein: a factor with many talents. Trends in Biochemical Sciences16:440–444
    [Google Scholar]
  12. Kónya J., Eklund C., af Geijersstam V., Yuan F., Stuber G., Dillner J.. 1997; Identification of a cytotoxic T-lymphocyte epitope in the human papillomavirus type 16 E2 protein. Journal of General Virology78:2615–2620
    [Google Scholar]
  13. Laga M., Icenogle J. P., Marsela R., Manoka A. T., Nzila N., Ryder R. W., Vermund S. H., Heyward W. L., Nelson A., Reeve W. C.. 1992; Genital papillomavirus infection and cervical dysplasia. Opportunistic complications of HIV infection. International Journal of Cancer50:45–48
    [Google Scholar]
  14. Maitland N. J., Conway S., Wilkinson N. S., Ramsdale J., Morris J. R., Sanders C. M., Burns J. E., Stern P. L., Wells M.. 1998; Expression patterns of the human papillomavirus type 16 transcription factor E2 in low- and high grade cervical intraepithelial neoplasia. Journal of Pathology186:275–280
    [Google Scholar]
  15. Man S.. 1998; Human cellular immune responses against human papillomaviruses in cervical neoplasia. Expert Reviews in Molecular Medicine , txt001smchttp://www-ermm.cbcu.cam.ac.uk
    [Google Scholar]
  16. Mann V. M., de Lao S. L., Brenes M., Brinton L. A., Rawls J. A., Green M., Reeves W. C., Rawls W. E.. 1990; Occurrence of IgA and IgG antibodies to select peptides representing human papillomavirus type 16 among cervical cancer cases and controls. Cancer Research50:7815–7819
    [Google Scholar]
  17. Matsukura T., Koi S., Sugase M.. 1989; Both episomal and integrated forms of human papillomavirus type 16 are involved in invasive cervical cancers. Virology172:63–72
    [Google Scholar]
  18. Morris J. D., Crook T., Bandara L. R., Davies R., LaThangue N. B., Vousden K. H.. 1993; Human papillomavirus type 16 E7 regulates E2F and contributes to mitogenic signalling. Oncogene8:893–898
    [Google Scholar]
  19. Nardelli-Hefliger D., Roden R. B. S., Benyacoub J., Sahli R., Kraehenbuhl J.-P., Schiller J. T., Lachat P., Potts A., De Grandi P.. 1997; Human papillomavirus type 16 virus-like particles expressed in attenuated Salmonella typhimurium elicit mucosal and systemic neutralizing antibodies in mice. Infection and Immunity65:3328–3336
    [Google Scholar]
  20. Reeves W. C., Rawls J. A., Green M., Rawls W. E.. 1990; Antibodies to human papillomavirus type 16 in patients with cervical neoplasia. Lancet335:551–552
    [Google Scholar]
  21. Remmink A. J., Walboomers J. M. M., Helmerhorst T. J. M., Voorhorst F. J., Rozendaal L., Risse E. K. J., Meijer C. J. L. M., Kenemans P.. 1995; The presence of persistent high-risk HPV genotypes in dysplastic cervical lesions is associated with progressive disease: natural history up to 36 months. International Journal of Cancer61:306–311
    [Google Scholar]
  22. Rocha-Zavaleta L., Jordan D., Pepper S., Corbitt G., Clarke F., Maitland N. J., Sanders C. M., Arrand J. R., Stern P. L., Stacey S. N.. 1997; Differences in serological IgA responses to recombinant baculovirus-derived human papillomavirus E2 protein in the natural history of cervical neoplasia. British Journal of Cancer75:1144–1150
    [Google Scholar]
  23. Sanders C. M., Stern P. L., Maitland N. J.. 1995; Characterization of human papillomavirus type 16 E2 protein and subdomains expressed in insect cells. Virology211:418–433
    [Google Scholar]
  24. Schafer A., Friemann W., Mielke M., Schwatlander B., Koch M. A.. 1991; The increased frequency of cervical dysplasia in women infected with the human immunodeficiency virus is related to the degree of immunosuppression. American Journal of Obstetrics and Gynaecology164:593–599
    [Google Scholar]
  25. Schwarz E., Freese U. K., Gissmann L., Mayer W., Roggenbuck B., Stremlau A., zur Hausen H.. 1985; Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature314:111–114
    [Google Scholar]
  26. Selvakumar R., Borenstein L. A., Lin Y. L., Ahmed R., Wettstein F. O.. 1995; Immunization with nonstructural proteins E1 and E2 of cottontail rabbit papillomavirus stimulates regression of virus-induced papillomas. Journal of Virology69:602–605
    [Google Scholar]
  27. Slebos R. J. C., Kessis T. D., Chen A. W., Han S. M., Hedrick L., Cho K. R.. 1995; Functional consequences of directed mutations in human papillomavirus E6 proteins: abrogation of p53-mediated cell cycle arrest correlates with p53 binding and degradation in vitro. Virology208:111–120
    [Google Scholar]
  28. Tindle R. W.. 1996; Human papillomavirus vaccines for cervical cancer. Current Opinions in Immunology8:643–650
    [Google Scholar]
  29. Ushikai M., Lace M. J., Yamakawa Y., Kono M., Anson J., Ishiji T., Parkkinen S., Wicker N., Valentine M. E., Davidson I.. and others 1994; Trans activation by the full-length E2 proteins of human papillomavirus type 16 and bovine papillomavirus type 1 in vitro and in vivo: cooperation with activation domains of cellular transcription factors. Journal of Virology68:6655–6666
    [Google Scholar]
  30. Yee C., Krishnan-Hewlett I., Baker C. C., Schlegel R., Howley P. M.. 1985; Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. American Journal of Pathology119:361–366
    [Google Scholar]
  31. Zinkernagel R. M.. 1996; Immunology taught by viruses. Science271:173–178
    [Google Scholar]
  32. Zur Hausen H.. 1994; Molecular pathogenesis of cancer of the cervix and its causation by specific human papillomavirus types. In Human Pathogenic Papillomaviruses. Current Topics in Microbiology and Immunology pp131–156 Edited by Zur Hausen H.. Berlin: Springer Verlag;
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-80-9-2453
Loading
/content/journal/jgv/10.1099/0022-1317-80-9-2453
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error