Original Article

Journal of Investigative Dermatology (1993) 101, 227–231; doi:10.1111/1523-1747.ep12364825

Skin Test to Assess Immunity Against Cottontail Rabbit Papillomavirus Antigens in Rabbits with Progressing Papillomas or After Papilloma Regression

Reinhard M Höpfl1, Neil D Christensen2, Michael G Angell3 and John W Kreider2,3

  1. 1Department of Dermatology and Venereology, University of Innsbruck, Innsbruck, Austria
  2. 2Department of Pathology, Pennsylvania State University, Hershey, PA, USA
  3. 3Department of Microbiology and Immunology, Pennsylvania State University, Hershey, PA, USA

Received 21 December 1992; Accepted 30 March 1993.

Top

Abstract

This study analyzed in vivo antiviral cellular immune reactions in the Shope rabbit papilloma – carcinoma model. Antigens studied in experimentally infected domestic rabbits were cottontail rabbit papillomavirus particles produced with the athymic (nu\nu) mouse xenograft system and bacterial fusion proteins containing the major or minor capsid protein. Recall reactions to antigens were tested by classic intracutaneous tests. Positive reactions had a biphasic course. Histopathology of skin test biopsy specimens showed infiltrating polymorphonuclear cells during the early stages. Later they were replaced by predominantly perivascular infiltrates composed of mononuclear cells. Time course of swelling and infiltrates resembled a delayed-type hypersensitivity reaction. Ten of 11 regressor rabbits (p = 0.00006) and 10 of 20 progressors (p = 0.009) had positive skin tests with intact and/or denaturated virus particles and individual capsid proteins also could elicit specific skin reactions. Skin reactivity to the cottontail rabbit papillomavirus particles was also greater (p = 0.042) in regressor rabbits (8 of 11) when compared to progressors (7 of 20). Recall reactions remained detectable at post-regression times, ranging from several months up to more than 2 years. We conclude that specific skin reactions against the cottontail rabbit papillomavirus in infected domestic rabbits exist, and are strongly positive to intact particles of this papillomavirus in animals (regressors) clinically free of disease.

Top

References

  1. Campo, MS: Vaccination against papillomavirus. Cancer Cells 1991 3: 421–426,
  2. Jarrett, WFH, Smith, KT, O'Neil, BW, Gaukroger, JM, Chandrachud, LM, Grindlay, GJ, McGarvie, GM, Campo, MS: Studies on vaccination against papillomaviruses: prophylactic and therapeutic vaccination with recombinant structural proteins. Virology 1991 184: 33–42,
  3. Morison, WL: Cell-mediated immune responses in patients with warts. Br J Dermatol 1975 93: 553–556,
  4. Crum, CP, Barber, S, Roche, JK: Pathobiology of papillomavirus-related cervical diseases: prospects for immunodiagnosis. Clin Microbiol Rev 1991 4: 270–285,
  5. Okabayashi, M, Angell, MG, Christensen, ND, J, W: Morphometric analysis and identification of infiltrating leucocytes in regressing and progressing Shope rabbit papillomas. Int J Cancer 1991 49: 919–923,
  6. Bavinck, JNB, Kootte, AMM, Van der Woude, FJ, Vandenbroucke, JP, Vermeer, BJ, Claas, FHJ: On a possible protective effect of HLA-A11 against skin cancer and keratotic skin lesions in renal transplant recipients. J Invest Dermatol 1991 97: 269–272,
  7. Wank, R, Thomssen, C: High risk of squamous cell carcinoma of the cervix for women with HLA-DQw3. Nature 1991 352: 723–724,  | Article | PubMed | ISI | ChemPort |
  8. Han, R, Breitburd, F, Marche, PN, Orth, G: Linkage of regression and malignant conversion of rabbit viral papillomas to MHC class II genes. Nature 1992 356: 66–68,  | Article |
  9. Strang, G, Hickling, JK, MeIndoe, GAJ, Howland, K, Wilkinson, D, Ikeda, H, Rothbard, JB: 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 71: 423–431,  | PubMed | ISI | ChemPort |
  10. Davies, DH, Hill, CM, Rothbard, JB, Chain, BM: Definition of murine T helper cell determinants in the major capsid protein of human papillomavirus type 16. J Gen Virol 1990 71: 2691–2698,
  11. Walter, M, Gissmann, L, Zentgraf, H, Kirchner, H: Measurement of cell-mediated immunity against bovine papilloma virus by lymphoproliferative reactions. Immunobiology 1987 174: 244–250,
  12. Cubie, HA, Norval, M, Crawford, L, Banks, L, Crook, T: Lymphoproliferative response to fusion proteins of human papillomaviruses in patients with cervical intraepithelial neoplasia. Epidemiol Infect 1990 103: 625–632,
  13. Viac, J, Thivolet, J, Chardonnet, Y: Specific immunity in patients suffering from recurring warts before and after repetitive intradermal tests with human papillomavirus. Br J Dermatol 1977 97: 365–370,
  14. Hausen, H: Papillomaviruses in anogenital cancer as a model to understand the role of viruses in human cancers. Cancer Res 1989 49: 4677–4681,
  15. Hopfl, R, Sandbichler, M, Sepp, N, Heim, K, Muller-Holzner, E, Wartusch, B, Dapunt, O, Jochmus-Kudielka, I, Ter Meulen, J, Gissmann, L, Fritsch, P: Skin test for HPV type 16 proteins in cervical intraepithelial neoplasia. Lancet 1991 337: 373–374,
  16. Kreider, J. W: Studies on the mechanism responsible for the spontaneous regression of the Shope rabbit papilloma. Cancer Res 1963 23: 1593–1599,
  17. Kreider, JW, Bartlett, GL: The Shope papilloma-carcinoma complex of rabbits: a model system of neoplastic progression and spontaneous regression. Adv Cancer Res 1981 35: 81–110,  | PubMed | ChemPort |
  18. Kreider, JW: Neoplastic progression of the Shope rabbit papilloma. In: Essex M, Todaro G, zur Hausen H, (eds.). Viruses in Naturally Occurring Cancers. Book A. Cold Spring Harbor Conference on Cell Proliferation 1980, 7: Cold Spring Harbor Press, Cold Spring Harbor, pp 283–299,
  19. Kreider, JW, Howett, MK, Leure-Dupree, AE, Zaino, RJ, Weber, JA: Laboratory production in vivo of infectious human papillomavirus type 11. J Virol 1987 61: 590–593,  | PubMed |
  20. Christensen, ND, Kreider, JW: Neutralization of CRPV infectivity by monoclonal antibodies that identify conformational epitopes on intact virions. Virus Res 1991 21: 169–179,
  21. Christensen, ND, Kreider, JW, Kan, NC, DiAngelo, SL: The open reading frame L2 of cottontail rabbit papillomavirus contains antibody-inducing neutralizing epitopes. Virology 1991 181: 572–579,
  22. Snippe, H, deReuver, MJ, Beunder, JW, van der Meer, JB, van Wichen, DF, Willers, JMN: Delayed-type hypersensitiviry in rabbits. Int Arch Allergy Immunol 1982 67: 139–144,
  23. vonBlomberg, M, Boerrigter, GH, Scheper, RJ: Interference of simultaneous skin tests in delayed hypersensitivity. Immunology 1978 35: 361–367,
  24. Jain, NC, (ed.) Schalm's Veterinary Hematology 1986 Lea & Febiger, Philadelphia,
  25. Coombs, PRA, Gell, PGH: Clinical Aspects of Immunology 1968 Blackwell Scientific, Oxford,
  26. Lindbom, L, Lundberg, C, Prieto, J, Raud, J, Nortamo, P, Gahmberg, CG, Patarroyo, M: Rabbit leukocyte adhesion molecules CD11/CD18 and their participation in acute and delayed inflammatory responses and leukocyte distribution in vivo. Clin Immunol Immunopathol 1990 57: 105–119,
  27. Kuramoto, Y, Tagami, H: Histopathologic pattern analysis of human intracutaneous tuberculin reaction. Am J Dermatopathol 1989 11: 329–337,
  28. 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: 655–659,  | Article | PubMed | ChemPort |
  29. Angell, MG, Christensen, ND, Kreider, JW: An in vitro system for studying the initial stages of cottontail rabbit papillomavirus (CRPV) infection. J Virol Methods 1992 39: 207–216,
  30. Naylor, MF, Neldner, KH, Yarbrough, GK, Rosio, TJ, Iriondo, M, Yeary, J: Contact immunotherapy of resistant warts. J Am Acad Dermatol 1988 19: 679–683,
  31. Mims, CA: The Pathogenesis of Infections Disease 1987, Academic Press, London, p 254,
  32. Moskophidis, D, Fang, L, Gossmann, J, Drjupin, R, Lohler, J, Bruns, M, Lehmann-Grube, F: Virus-specific delayed-type hypersensitiviry (DTH). Cells mediating lymphocytic choriomeningitis virus-specific DTH reaction in mice. J Immunol 1990 144: 1926–1934,  | PubMed |
  33. Kundig, TM, Althage, A, Hengartner, H, Zinkernagel, RM: Skin test to assess virus-specific cytotoxic T-cell activity. Proc Natl Acad Sci USA 1992 89: 7757–7761,

Extra navigation

.
ADVERTISEMENT