Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1997 Sep;71(9):6427–6432. doi: 10.1128/jvi.71.9.6427-6432.1997

Isolation and characterization of human papillomavirus type 6-specific T cells infiltrating genital warts.

K Hong 1, C E Greer 1, N Ketter 1, G Van Nest 1, X Paliard 1
PMCID: PMC191916  PMID: 9261360

Abstract

The potential role of T cells in the control of human papillomavirus type 6 (HPV-6) infections is an appealing premise, but their actual role has been sparsely investigated. Since HPV-6 infections are confined to the epithelium, such an investigation should focus on the T cells present at the site of infection (i.e., the warts). Therefore, we isolated wart-infiltrating lymphocytes (WIL) from patients with clinically diagnosed anogenital warts. These WIL were characterized by their phenotype and their specificity for E7 and L1 proteins of HPV-6. The phenotype of WIL varied drastically from patient to patient, as determined by their expression of CD4, CD8, T-cell receptor alpha/beta chain (TCR alpha beta), and TCR gamma delta. Despite this heterogeneity in phenotype, HPV-6 E7 and/or L1-specific WIL, as determined by lymphoproliferation, could be isolated from more than 75% of the patients studied. Among all L1 peptides recognized by WIL, peptides 311-330 and 411-430 were the most consistently detected, with seven of nine patients for whom L1 peptide reactivity was observed responding to at least one of them. Moreover, the HPV-6 epitopic peptides recognized by WIL differed to some extent from those recognized by peripheral T cells.

Full Text

The Full Text of this article is available as a PDF (173.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altmann A., Jochmus-Kudielka I., Frank R., Gausepohl H., Moebius U., Gissmann L., Meuer S. C. Definition of immunogenic determinants of the human papillomavirus type 16 nucleoprotein E7. Eur J Cancer. 1992;28(2-3):326–333. doi: 10.1016/s0959-8049(05)80047-4. [DOI] [PubMed] [Google Scholar]
  2. Bartholomew J. S., Stacey S. N., Coles B., Burt D. J., Arrand J. R., Stern P. L. Identification of a naturally processed HLA A0201-restricted viral peptide from cells expressing human papillomavirus type 16 E6 oncoprotein. Eur J Immunol. 1994 Dec;24(12):3175–3179. doi: 10.1002/eji.1830241239. [DOI] [PubMed] [Google Scholar]
  3. Bauer H. M., Ting Y., Greer C. E., Chambers J. C., Tashiro C. J., Chimera J., Reingold A., Manos M. M. Genital human papillomavirus infection in female university students as determined by a PCR-based method. JAMA. 1991 Jan 23;265(4):472–477. [PubMed] [Google Scholar]
  4. Bishop P. E., McMillan A., Fletcher S. An immunohistological study of spontaneous regression of condylomata acuminata. Genitourin Med. 1990 Apr;66(2):79–81. doi: 10.1136/sti.66.2.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brenner M. B., Strominger J. L., Krangel M. S. The gamma delta T cell receptor. Adv Immunol. 1988;43:133–192. [PubMed] [Google Scholar]
  6. Carter J. J., Wipf G. C., Hagensee M. E., McKnight B., Habel L. A., Lee S. K., Kuypers J., Kiviat N., Daling J. R., Koutsky L. A. Use of human papillomavirus type 6 capsids to detect antibodies in people with genital warts. J Infect Dis. 1995 Jul;172(1):11–18. doi: 10.1093/infdis/172.1.11. [DOI] [PubMed] [Google Scholar]
  7. Charleson F. C., Norval M., Benton E. C., Hunter J. A. Lymphoproliferative responses to human papillomaviruses in patients with cutaneous warts. Br J Dermatol. 1992 Dec;127(6):551–559. doi: 10.1111/j.1365-2133.1992.tb14864.x. [DOI] [PubMed] [Google Scholar]
  8. Coleman N., Birley H. D., Renton A. M., Hanna N. F., Ryait B. K., Byrne M., Taylor-Robinson D., Stanley M. A. Immunological events in regressing genital warts. Am J Clin Pathol. 1994 Dec;102(6):768–774. doi: 10.1093/ajcp/102.6.768. [DOI] [PubMed] [Google Scholar]
  9. Gassenmaier A., Fuchs P., Schell H., Pfister H. Papillomavirus DNA in warts of immunosuppressed renal allograft recipients. Arch Dermatol Res. 1986;278(3):219–223. doi: 10.1007/BF00412927. [DOI] [PubMed] [Google Scholar]
  10. Greer C. E., Wheeler C. M., Ladner M. B., Beutner K., Coyne M. Y., Liang H., Langenberg A., Yen T. S., Ralston R. Human papillomavirus (HPV) type distribution and serological response to HPV type 6 virus-like particles in patients with genital warts. J Clin Microbiol. 1995 Aug;33(8):2058–2063. doi: 10.1128/jcm.33.8.2058-2063.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Groh V., Porcelli S., Fabbi M., Lanier L. L., Picker L. J., Anderson T., Warnke R. A., Bhan A. K., Strominger J. L., Brenner M. B. Human lymphocytes bearing T cell receptor gamma/delta are phenotypically diverse and evenly distributed throughout the lymphoid system. J Exp Med. 1989 Apr 1;169(4):1277–1294. doi: 10.1084/jem.169.4.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hannet I., Erkeller-Yuksel F., Lydyard P., Deneys V., DeBruyère M. Developmental and maturational changes in human blood lymphocyte subpopulations. Immunol Today. 1992 Jun;13(6):215–218. doi: 10.1016/0167-5699(92)90157-3. [DOI] [PubMed] [Google Scholar]
  13. Heim K., Christensen N. D., Hoepfl R., Wartusch B., Pinzger G., Zeimet A., Baumgartner P., Kreider J. W., Dapunt O. Serum IgG, IgM, and IgA reactivity to human papillomavirus types 11 and 6 virus-like particles in different gynecologic patient groups. J Infect Dis. 1995 Aug;172(2):395–402. doi: 10.1093/infdis/172.2.395. [DOI] [PubMed] [Google Scholar]
  14. Höpfl R., Sandbichler M., Sepp N., Heim K., Müller-Holzner E., Wartusch B., Dapunt O., Jochmus-Kudielka I., ter Meulen J., Gissmann L. Skin test for HPV type 16 proteins in cervical intraepithelial neoplasia. Lancet. 1991 Feb 9;337(8737):373–374. doi: 10.1016/0140-6736(91)91014-l. [DOI] [PubMed] [Google Scholar]
  15. Iwatsuki K., Tagami H., Takigawa M., Yamada M. Plane warts under spontaneous regression. Immunopathologic study on cellular constituents leading to the inflammatory reaction. Arch Dermatol. 1986 Jun;122(6):655–659. doi: 10.1001/archderm.122.6.655. [DOI] [PubMed] [Google Scholar]
  16. Johnson J. C., Burnett A. F., Willet G. D., Young M. A., Doniger J. High frequency of latent and clinical human papillomavirus cervical infections in immunocompromised human immunodeficiency virus-infected women. Obstet Gynecol. 1992 Mar;79(3):321–327. doi: 10.1097/00006250-199203000-00001. [DOI] [PubMed] [Google Scholar]
  17. Kadish A. S., Romney S. L., Ledwidge R., Tindle R., Fernando G. J., Zee S. Y., Van Ranst M. A., Burk R. D. Cell-mediated immune responses to E7 peptides of human papillomavirus (HPV) type 16 are dependent on the HPV type infecting the cervix whereas serological reactivity is not type-specific. J Gen Virol. 1994 Sep;75(Pt 9):2277–2284. doi: 10.1099/0022-1317-75-9-2277. [DOI] [PubMed] [Google Scholar]
  18. Kaufmann S. H. gamma/delta and other unconventional T lymphocytes: what do they see and what do they do? Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2272–2279. doi: 10.1073/pnas.93.6.2272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Luxton J. C., Rowe A. J., Cridland J. C., Coletart T., Wilson P., Shepherd P. S. Proliferative T cell responses to the human papillomavirus type 16 E7 protein in women with cervical dysplasia and cervical carcinoma and in healthy individuals. J Gen Virol. 1996 Jul;77(Pt 7):1585–1593. doi: 10.1099/0022-1317-77-7-1585. [DOI] [PubMed] [Google Scholar]
  20. Melbye M., Palefsky J., Gonzales J., Ryder L. P., Nielsen H., Bergmann O., Pindborg J., Biggar R. J. Immune status as a determinant of human papillomavirus detection and its association with anal epithelial abnormalities. Int J Cancer. 1990 Aug 15;46(2):203–206. doi: 10.1002/ijc.2910460210. [DOI] [PubMed] [Google Scholar]
  21. Modlin R. L., Pirmez C., Hofman F. M., Torigian V., Uyemura K., Rea T. H., Bloom B. R., Brenner M. B. Lymphocytes bearing antigen-specific gamma delta T-cell receptors accumulate in human infectious disease lesions. Nature. 1989 Jun 15;339(6225):544–548. doi: 10.1038/339544a0. [DOI] [PubMed] [Google Scholar]
  22. Porreco R., Penn I., Droegemueller W., Greer B., Makowski E. Gynecologic malignancies in immunosuppressed organ homograft recipients. Obstet Gynecol. 1975 Apr;45(4):359–364. [PubMed] [Google Scholar]
  23. Sadovnikova E., Stauss H. J. T cell epitopes in human papilloma virus proteins. Behring Inst Mitt. 1994 Jul;(94):87–93. [PubMed] [Google Scholar]
  24. Sciammas R., Johnson R. M., Sperling A. I., Brady W., Linsley P. S., Spear P. G., Fitch F. W., Bluestone J. A. Unique antigen recognition by a herpesvirus-specific TCR-gamma delta cell. J Immunol. 1994 Jun 1;152(11):5392–5397. [PubMed] [Google Scholar]
  25. Shepherd P. S., Rowe A. J., Cridland J. C., Coletart T., Wilson P., Luxton J. C. Proliferative T cell responses to human papillomavirus type 16 L1 peptides in patients with cervical dysplasia. J Gen Virol. 1996 Apr;77(Pt 4):593–602. doi: 10.1099/0022-1317-77-4-593. [DOI] [PubMed] [Google Scholar]
  26. Steele J. C., Stankovic T., Gallimore P. H. Production and characterization of human proliferative T-cell clones specific for human papillomavirus type 1 E4 protein. J Virol. 1993 May;67(5):2799–2806. doi: 10.1128/jvi.67.5.2799-2806.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stoler M. H., Wolinsky S. M., Whitbeck A., Broker T. R., Chow L. T. Differentiation-linked human papillomavirus types 6 and 11 transcription in genital condylomata revealed by in situ hybridization with message-specific RNA probes. Virology. 1989 Sep;172(1):331–340. doi: 10.1016/0042-6822(89)90135-9. [DOI] [PubMed] [Google Scholar]
  28. Stone K. M. Human papillomavirus infection and genital warts: update on epidemiology and treatment. Clin Infect Dis. 1995 Apr;20 (Suppl 1):S91–S97. doi: 10.1093/clinids/20.supplement_1.s91. [DOI] [PubMed] [Google Scholar]
  29. Strang G., Hickling J. K., McIndoe G. A., Howland K., Wilkinson D., Ikeda H., Rothbard J. B. Human T cell responses to human papillomavirus type 16 L1 and E6 synthetic peptides: identification of T cell determinants, HLA-DR restriction and virus type specificity. J Gen Virol. 1990 Feb;71(Pt 2):423–431. doi: 10.1099/0022-1317-71-2-423. [DOI] [PubMed] [Google Scholar]
  30. Tagami H., Oguchi M., Ofuji S. Immunological aspects of wart regression with special reference to regression phenomenon of numerous flat warts. An experiment on tumor immunity in man by nature. J Dermatol. 1983 Feb;10(1):1–12. doi: 10.1111/j.1346-8138.1983.tb01098.x. [DOI] [PubMed] [Google Scholar]
  31. Tarpey I., Stacey S., Hickling J., Birley H. D., Renton A., McIndoe A., Davies D. H. Human cytotoxic T lymphocytes stimulated by endogenously processed human papillomavirus type 11 E7 recognize a peptide containing a HLA-A2 (A*0201) motif. Immunology. 1994 Feb;81(2):222–227. [PMC free article] [PubMed] [Google Scholar]
  32. Wikström A., van Doornum G. J., Kirnbauer R., Quint W. G., Dillner J. Prospective study on the development of antibodies against human papillomavirus type 6 among patients with condyloma acuminata or new asymptomatic infection. J Med Virol. 1995 Aug;46(4):368–374. doi: 10.1002/jmv.1890460413. [DOI] [PubMed] [Google Scholar]
  33. Wikström A., van Doornum G. J., Quint W. G., Schiller J. T., Dillner J. Identification of human papillomavirus seroconversions. J Gen Virol. 1995 Mar;76(Pt 3):529–539. doi: 10.1099/0022-1317-76-3-529. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES