Regression of canine oral papillomas is associated with infiltration of CD4+ and CD8+ lymphocytes.

Canine oral papillomavirus (COPV) infection is used in vaccine development against mucosal papillomaviruses. The predictable, spontaneous regression of the papillomas makes this an attractive system for analysis of cellular immunity. Immunohistochemical analysis of the timing and phenotype of immune cell infiltration revealed a marked influx of leukocytes during wart regression, including abundant CD4+ and CD8+ cells, with CD4+ cells being most numerous. Comparison of these findings, and those of immunohistochemistry using TCRalphabeta-, TCRgammadelta-, CD1a-, CD1c-, CD11a-, CD11b-, CD11c-, CD18-, CD21-, and CD49d-specific monoclonal antibodies, with previously published work in the human, ox, and rabbit models revealed important differences between these systems. Unlike bovine papillomavirus lesions, those of COPV do not have a significant gamma/delta T-cell infiltrate. Furthermore, COPV lesions had numerous CD4+ cells, unlike cottontail rabbit papillomavirus lesions. The lymphocyte infiltrate in the dog resembled that in human papillomavirus lesions, indicating that COPV is an appropriate model for human papillomavirus immunity.

[1]  D. Williams,et al.  Studies of canine leucocyte antigens: a significant advance in canine immunology. , 1997, Veterinary journal.

[2]  N. Jain Essentials of Veterinary Hematology , 1993 .

[3]  T. Olivry,et al.  Molecular cloning of canine bullous pemphigoid antigen 2 cDNA and immunomapping of NC16A domain by canine bullous pemphigoid autoantibodies. , 2000, Biochimica et biophysica acta.

[4]  M. Stanley Replication of human papillomaviruses in cell culture. , 1994, Antiviral research.

[5]  J. Peto,et al.  Human papillomavirus is a necessary cause of invasive cervical cancer worldwide , 1999, The Journal of pathology.

[6]  M. Campo Vaccination against papillomavirus in cattle. , 1997, Current topics in microbiology and immunology.

[7]  D. Rigal,et al.  Abnormalities of lymphocyte subsets in canine systemic lupus erythematosus. , 1995, Autoimmunity.

[8]  R. Ahmed,et al.  Regression of papillomas induced by cottontail rabbit papillomavirus is associated with infiltration of CD8+ cells and persistence of viral DNA after regression , 1997, Journal of virology.

[9]  C. Mackay,et al.  Prominence of gamma delta T cells in the ruminant immune system. , 1991, Immunology today.

[10]  A. Ferenczy,et al.  Therapeutic approaches to genital warts. , 1997, The American journal of medicine.

[11]  R. Storb,et al.  Organization of the canine major histocompatibility complex: current perspectives. , 1999, The Journal of heredity.

[12]  S. Tonegawa,et al.  Gamma/delta cells. , 1993, Annual review of immunology.

[13]  C. Cluff,et al.  Differential distribution of γδT-cell receptor lymphocyte subpopulations in blood and spleen of young and adult cattle , 1994 .

[14]  T. Starzl History of Clinical Transplantation , 2000, World Journal of Surgery.

[15]  R. Yu,et al.  T lymphocytes bearing the γδ T‐cell receptor: a study in normal human skin and pathological skin conditions , 1992 .

[16]  C. Cluff,et al.  Differential distribution of gamma delta T-cell receptor lymphocyte subpopulations in blood and spleen of young and adult cattle. , 1994, Veterinary immunology and immunopathology.

[17]  D. Danilenko,et al.  Monoclonal antibodies specific for canine CD4 and CD8 define functional T-lymphocyte subsets and high-density expression of CD4 by canine neutrophils. , 1992, Tissue antigens.

[18]  J. Palefsky,et al.  Prevalence and risk factors for human papillomavirus infection of the anal canal in human immunodeficiency virus (HIV)-positive and HIV-negative homosexual men. , 1998, The Journal of infectious diseases.

[19]  L. Chow,et al.  In vitro experimental systems for HPV: epithelial raft cultures for investigations of viral reproduction and pathogenesis and for genetic analyses of viral proteins and regulatory sequences. , 1997, Clinics in dermatology.

[20]  M. Campo,et al.  Phenotypical characterization of lymphocytes infiltrating regressing papillomas , 1996, Journal of virology.

[21]  M. Stanley,et al.  Naturally occurring, nonregressing canine oral papillomavirus infection: host immunity, virus characterization, and experimental infection. , 1999, Virology.

[22]  M. Stanley,et al.  Canine papillomavirus--A centenary review. , 1999, Journal of comparative pathology.

[23]  N. Christensen,et al.  Morphometric analysis and identification of infiltrating leucocytes in regressing and progressing shope rabbit papillomas , 1991, International journal of cancer.

[24]  D. Danilenko,et al.  Canine leukocyte integrins: characterization of a CD18 homologue. , 1990, Tissue antigens.

[25]  M. Stanley,et al.  Immunological events in regressing genital warts. , 1994, American journal of clinical pathology.

[26]  H. B. Lim,et al.  In vitro synthesis of oncogenic human papillomaviruses requires episomal genomes for differentiation-dependent late expression. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[27]  R. A. Hope Oxford Handbook of Clinical Medicine , 1985 .

[28]  H. Ochs,et al.  B-cell function in canine X-linked severe combined immunodeficiency. , 1998, Veterinary immunology and immunopathology.

[29]  A. Singer,et al.  Differential regulation of HLA-DQ expression by keratinocytes and Langerhans cells in normal and premalignant cervical epithelium. , 1998, Tissue antigens.

[30]  C. Meyers,et al.  Biosynthesis of human papillomavirus from a continuous cell line upon epithelial differentiation. , 1992, Science.

[31]  C. Evans,et al.  Canine oral papillomatosis. II. Immunologic aspects of the disease. , 1960, Cancer research.

[32]  C. Mackay,et al.  Prominence of γδ T cells in the ruminant immune system , 1991 .

[33]  B. Hartnett,et al.  Canine X-linked severe combined immunodeficiency , 1998, Immunologic research.

[34]  R. Storb,et al.  Canine models of bone marrow transplantation. , 1990, Laboratory animal science.

[35]  W. White,et al.  In Vitro Infection and Type-Restricted Antibody-Mediated Neutralization of Authentic Human Papillomavirus Type 16 , 1998, Journal of Virology.

[36]  D. Danilenko,et al.  Canine leukocyte cell adhesion molecules (LeuCAMs): characterization of the CD11/CD18 family. , 1992, Tissue antigens.

[37]  S. Metcalfe,et al.  Monoclonal antibodies that define canine homologues of human CD antigens: summary of the First International Canine Leukocyte Antigen Workshop (CLAW). , 1994, Tissue antigens.

[38]  T. Kindt,et al.  Selection of rabbit CD4- CD8- T cell receptor-gamma/delta cells by in vitro transformation with human T lymphotropic virus-I , 1993, The Journal of experimental medicine.

[39]  R. Schlegel,et al.  A formalin-inactivated vaccine protects against mucosal papillomavirus infection: a canine model. , 1994, Pathobiology : journal of immunopathology, molecular and cellular biology.

[40]  R. Batt,et al.  Development of wheat-sensitive enteropathy in Irish Setters: morphologic changes. , 1990, American journal of veterinary research.

[41]  H. Bazin,et al.  Handbook of vertebrate immunology. , 1998 .

[42]  M. Stanley,et al.  Human papillomaviruses and cervical cancer : biology and immunology , 1994 .