Skip to main content

Advertisement

SpringerLink
Log in

Functional characterization of CD4 and CD8 T cell responses among human papillomavirus infected patients with ano-genital warts

  • Original Article
  • Published:
VirusDisease Aims and scope Submit manuscript

Abstract

Ano-genital warts are considered one of the commonest and highly infectious sexually transmitted infections. These warts are primarily caused by the human papillomavirus (HPV) of the family Papillomaviridae, genus alpha-papillomavirus, species 10 and types 6 and 11. However the high recurrence rate of warts is a matter of serious concern to the patients and a challenge for the treating physician. The conventional treatment options are targeted only to the local site of warts. There is no systemic treatment modality as there is limited understanding of the disease immune-pathogenesis. The role of cell-mediated immunity in combating HPV infection is not clearly defined. Hence the present study is aimed at investigating the CD4+ T helper (Th1 and Th2) and CD8+ T cell responses among wart patients. In this study, we compared HPV6 and HPV11 antigen-specific T cell responses among venereal wart patients relative to healthy controls. Significant decrease in percent frequencies of IFN-γ producing CD4+ and CD8+ T cells were observed in HPV infected wart patients. On the other hand, the frequency of CD4+ T cells expressing IL-4 was significantly increased in these patients as compared to healthy controls. The observed functional skewing of HPV specific T cells from Th1 to Th2 response in patients indicated suppressed immunity against the HPV. Moreover, decrease in CD8 T cell function correlated with poor wart clearance. Our findings open future avenues for exploring potential immunomodulation strategies as an adjunct to standard treatment for better management of these patients and prevention of recurrence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Al-Saeed IAM, Al-Saadi MAK, Ewadh WAA. Immunological study on genital wart patients in Babylon Province-Iraq. Med J Babylon 2015; 12(1):233–39.

    Google Scholar 

  2. Amador-Molina A, Hernández-Valencia JF, Lamoyi E, Contreras-Paredes A, Lizano M. Role of innate immunity against human papillomavirus (HPV) infections and effect of adjuvants in promoting specific immune response. Viruses. 2013;5:2624–42.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Barnard P, McMillan NA. The human papillomavirus E7 oncoprotein abrogates signaling mediated by interferon-alpha. Virology. 1999;259:305–13.

    Article  CAS  PubMed  Google Scholar 

  4. Benton C, Shahdullah H, Hunter JAA. Human papillomavirus in the immunocompromised. Papillomavirus Rep. 1992;3:23–6.

    Google Scholar 

  5. Brodell LA, Mercurio MG, Brodell RT. The diagnosis and treatment of human papillomavirus-mediated genital lesions. Cutis. 2007;79:5–10.

    PubMed  Google Scholar 

  6. Broomall EM, Reynolds SM, Jacobson RM. Epidemiology, clinical manifestations, and recent advances in vaccination against human papillomavirus. Postgrad Med. 2010;122(2):121–9.

    Article  PubMed  Google Scholar 

  7. Cao Y, Zhao J, Lei Z, Shen S, Liu C, Li D, Liu J, Shen GX, Zhang GM, Feng ZH, et al. Local accumulation of FOXP3+ regulatory T cells: evidence for an immune evasion mechanism in patients with large condylomata acuminate. J Immunol. 2008;180:7681–6.

    Article  CAS  PubMed  Google Scholar 

  8. Castellsague X, Ghaffari A, Daniel RW, Bosch FX, Munoz N, Shah KV. Prevalence of penile human papillomavirus DNA in husbands of women with and without cervical neoplasia: a study in Spain and Colombia. J Infect Dis. 1997;176:353–61. doi:10.1086/514052.

    Article  CAS  PubMed  Google Scholar 

  9. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines. MMWR. 2006;55(No.RR-11):62–7.

    Google Scholar 

  10. Clerici M, Merola M, Ferrario E. Cytokine production patterns in cervical intraepithelial neoplasia: association with human papillomavirus infection. J Natl Cancer Inst. 1997;89(3):245–50.

    Article  CAS  PubMed  Google Scholar 

  11. Coleman N, Birley HD, Renton AM, et al. Immunological events in regressing genital warts. Am J Clin Pathol. 1994;102:768–74.

    Article  CAS  PubMed  Google Scholar 

  12. Critchlow CW, Holmes KK, Wood R, Krueger L, Dunphy C, Vernon DA, Daling JR, Kiviat NB. Association of human immunodeficiency virus and anal human papillomavirus infection among homosexual men. Arch Intern Med. 1992;152:1673–6.

    Article  CAS  PubMed  Google Scholar 

  13. Critchlow CW, Hawes SE, Kuypers JM, Goldbaum GM, Holmes KK, Surawicz CM, Kiviat NB. Effect of HIV infection on the natural history of anal human papillomavirus infection. AIDS. 1998;12:1177–84.

    Article  CAS  PubMed  Google Scholar 

  14. De Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H. Classification of papillomaviruses. Virology. 2004;324(1):17–27.

    Article  PubMed  Google Scholar 

  15. Devoti J, Hatam L, Lucs A, Afzal A, Abramson A, Steinberg B, Bonagura V. Decreased langerhans cell responses to IL-36γ: altered innate immunity in patients with recurrent respiratory papillomatosis. Mol Med. 2014;20:372–80.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Einhorn N, Ling P, Strander H. Systemic interferon alpha treatment of human condylomata acuminata. Acta Obstet Gynecol Scand. 1983;62:285–7.

    Article  CAS  PubMed  Google Scholar 

  17. Elliot J, Androphy DRL. Warts. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, editors. Fitzpatrick’s dermatology in general medicine. 7th ed. New York: McGraw-Hill; 2008. p. 1914–22.

    Google Scholar 

  18. Fairley CK, Chen S, Tabrizi SN, McNeil J, Becker G, Walker R, Atkins RC, Thomson N, Allan P, Woodburn C, et al. Prevalence of HPV DNA in cervical specimens in women with renal transplants: a comparison with dialysis-dependent patients and patients with renal impairment. Nephrol Dial Transplant. 1994;9:416–20.

    CAS  PubMed  Google Scholar 

  19. Feng JY, Peng ZH, Tang XP, Geng SM, Liu YP. Immunohistochemical and ultrastructural features of langerhans cells in condyloma acuminatum. J Cutan Pathol. 2008;35:15–20.

    PubMed  Google Scholar 

  20. Gall SA, Hughes CE, Trofatter K. Interferon for the therapy of condyloma acuminatum. Am J Obstet Gynecol. 1985;153:157–63.

    Article  CAS  PubMed  Google Scholar 

  21. Garcia-Lora A, Algarra I, Garrido F. MHC class I antigens, immune surveillance, and tumor immune escape. J Cell Physiol 2003;195(3):346–55.

    Article  CAS  PubMed  Google Scholar 

  22. Giuliano AR, Tortolero-Luna G, Ferrer E, Burchell AN, de Sanjose S, Kjaer SK, Munoz N, Schiffman M, Bosch FX. Epidemiology of human papillomavirus infection in men, cancers other than cervical and benign conditions. Vaccine. 2008;26(Suppl 10):K17–28.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Graziottin A, Serafini A. HPV infection in women: psychosexual impact of genital warts and intraepithelial lesions. J Sex Med. 2009;6:633–45. doi:10.1111/j.1743-6109.2008.01151.

    Article  PubMed  Google Scholar 

  24. Greer CE, Wheeler CM, Ladner MB, et al. Human papillomavirus (HPV) type distribution and serological response to HPV type 6 virus-like particles in patients with genital warts. J Clin Microbiol. 1995;33(8):2058–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Gross G, Pfister H. Role of human papillomavirus in penile cancer, penile intraepithelial squamous cell neoplasias and in genital warts. Med MicrobiolImmunol (Berl). 2004;193:35–44. doi:10.1007/s00430-003-0181-2.

    Article  CAS  Google Scholar 

  26. 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;122:655–9.

    Article  CAS  PubMed  Google Scholar 

  27. Kim J, Modlin RL, Moy RL, et al. IL-10 production in cutaneous basal and squamous cell carcinomas. A mechanism for evading the local T-cell immune response. J Immunol. 1995;155:2240–7.

    CAS  PubMed  Google Scholar 

  28. Kodner CM, Nasraty S. Management of genital warts. Am Fam Physician. 2004;70:2335–42.

    PubMed  Google Scholar 

  29. Lacey CJ, Lowndes CM, Shah KV. Chapter 4: Burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine. 2006;24(Issue 3):35–41.

    Article  Google Scholar 

  30. Lombard I, et al. Human papillomavirus genotype as a major determinant of the course of cervical cancer. J Clin Oncol. 1998;16(8):2613–9.

    Article  CAS  PubMed  Google Scholar 

  31. Maw RD, Reitano M, Roy M. An international survey of patients with genital warts: perceptions regarding treatment and impact on lifestyle. Int J STD AIDS. 1998;9:571–8. doi:10.1258/0956462981921143.

    Article  CAS  PubMed  Google Scholar 

  32. Milner DA. Diagnostic pathology: infectious diseases. Amsterdam: Elsevier Health Sciences; 2015. p. 40.

    Google Scholar 

  33. Mohanty KC, Scott CS. Immunotherapy of genital warts with inosine pranobex (Imunovir): preliminary study. Genitourin Med. 1986;62:352–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Morelli AE, Belardi G, DiPaola G, Paredes A, Fainboim L. Cellular subsets and epithelial ICAM-1 and HLA-DR expression in human papillomavirus infection of the vulva. Acta Derm Venereol. 1994;74:45–50.

    CAS  PubMed  Google Scholar 

  35. Narayanan B. A retrospective study of the pattern of sexually transmitted diseases during a ten-year period. Indian J Dermatol Venereol Leprol. 2005;71:333–7.

    Article  PubMed  Google Scholar 

  36. Peghini BC, Abdalla DR, Barcelos AC, Teodoro L, Murta EF, Michelin MA. Local cytokine profiles of patients with cervical intraepithelial and invasive neoplasia. Hum Immunol. 2012;73(9):920–6.

    Article  CAS  PubMed  Google Scholar 

  37. Sasagawa T, Takagi H, Makinoda S. Immune response against human papillomavirus (HPV) infection and evasion of host defense in cervical cancer. J Infect Chemother. 2012;18:807–15.

    Article  CAS  PubMed  Google Scholar 

  38. Scheinfeld N, Lehman DS. An evidence-based review of medical and surgical treatments of genital warts. Dermatol Online J. 2006;12:5.

    PubMed  Google Scholar 

  39. Schneider A, Papendick U, Gissmann L, De Villiers EM. Interferon treatment of human genital papillomavirus infection: importance of viral type. Int J Cancer. 1987;40:610–4.

    Article  CAS  PubMed  Google Scholar 

  40. Sillman F, Stanek A, Sedlis A, Rosenthal J, Lanks KW, Buchhagen D, Nicastri A, Boyce J. The relationship between human papillomavirus and lower genital intraepithelial neoplasia in immunosuppressed women. Am J Obstet Gynecol. 1984;150:300–8.

    Article  CAS  PubMed  Google Scholar 

  41. Stanley M. Immunobiology of HPV and HPV vaccines. Gynecol Oncol. 2008;109(Suppl. S2):15–21.

    Article  Google Scholar 

  42. Tay EH, Garland S, Tang G, Nolan T, Huang LM, Orloski L, Lu S, Barr E. Clinical trial experience with prophylactic HPV 6/11/16/18 VLP vaccine in young women from the Asia-Pacific region. Int J Gynaecol Obstet. 2008;102:275–83. doi:10.1016/j.ijgo.2008.03.021.

    Article  CAS  PubMed  Google Scholar 

  43. Tzellos TG, Sardeli C, Lallas A, Papazisis G, Chourdakis M, Kouvelas D. Efficacy, safety and tolerability of green tea catechins in the treatment of external anogenital warts: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2011;25:345–53. doi:10.1111/j.1468-3083.2010.03796.

    Article  CAS  PubMed  Google Scholar 

  44. von Krogh G, Lacey CJ, Gross G, Barrasso R, Schneider A. European guideline for the management of anogenital warts. Int J STD AIDS. 2001;12(Suppl 3):40–7.

    Google Scholar 

  45. Wiley DJ, Douglas J, Beutner K, Cox T, Fife K, Moscicki AB, Fukumoto L. External genital warts: diagnosis, treatment, and prevention. Clin Infect Dis. 2002;35(Suppl 2):S210–24.

    Article  CAS  PubMed  Google Scholar 

  46. Xu Y, Zhu KJ, Zhu N, Jiang DH, Chen XZ, Cheng H. Expression of Foxp3+CD4+CD25+ regulatory T cells and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of patients with condyloma acuminatum. Clin Exp Dermatol. 2009;34(2):229–35.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors hereby acknowledge the valuable contribution of Junior and Senior Residents of Department of Dermatology, Dr. Ram Manohar Lohia Hospital, New Delhi for patient recruitment, Mr. N.P. Singh and Mr. Pankaj, Lab. technician, Abhinav Saurabh, Prabin and Girija, SRF, Department of Transplant Immunology and Immunogenetics, AIIMS for their laboratory support and Dr. Abha Agrawal, Former Scientist ‘F’, National Institute of Medical Statistics, New Delhi for statistical analysis.

Author information

Author notes

  1. Dipendra Kumar Mitra

    Present address: Max Super Specialty Hospital, Saket, New Delhi, India

Authors and Affiliations

  1. Indian Council of Medical Research, Room No. 311, V Ramalingaswami Bhawan, New Delhi, 110029, India

    Manjula Singh

  2. Department of Transplant Immunology & Immunogenetics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Deepshi Thakral & Dipendra Kumar Mitra

  3. Amity Institute of Virology & Immunology, Amity University, Noida, Uttar Pradesh, India

    Narayan Rishi

  4. Max Super Specialty Hospital, Saket, New Delhi, India

    Hemanta Kumar Kar

Authors
  1. Manjula Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deepshi Thakral
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Narayan Rishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hemanta Kumar Kar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dipendra Kumar Mitra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dipendra Kumar Mitra.

Additional information

Hemanta Kumar Kar formerly affiliated at Dr. Ram Manohar Lohia Hospital, Baba Kharak Singh Marg, New Delhi 110001, India.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Singh, M., Thakral, D., Rishi, N. et al. Functional characterization of CD4 and CD8 T cell responses among human papillomavirus infected patients with ano-genital warts. VirusDis. 28, 133–140 (2017). https://doi.org/10.1007/s13337-017-0382-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13337-017-0382-8

Keywords

Search

Navigation