Immunological events in regressing genital warts.

Little is known of the in vivo role of the immune system in controlling human papillomavirus infection in the genital tract. The authors have studied 125 closely monitored patients with genital warts. Of these 125 patients, wart regression was seen in 28 patients. This study provides evidence that clearance of human papillomavirus from the genital tract is characterized by an active cell-mediated immune response. Regressing warts (n = 14) contained significantly more T lymphocytes (P < .05, Wilcoxon rank sum test) and macrophages (P < .01) than did nonregressing controls (n = 14). CD4-positive lymphocytes predominated in regression, both within the wart stroma and the surface epithelium, where there was a significant change in the ratio of CD4+ to CD8+ cells (P < .01). Lymphocytes in regression also showed greater expression of activation markers, and the majority were of the "antigen-experienced" phenotype. There was no difference in Langerhans cell numbers, although there was significant induction of the immune accessory molecules HLA-DR and ICAM1 (P < .05) on keratinocytes, and E-selectin and VCAM1 (P < .05) on endothelial cells in regressing warts. The changes in regression are consistent with a delayed-type hypersensitivity reaction to foreign antigen, and the ability to induce and mount such a response may be a critical determinant of effective natural immunity to the genital HPVs. Specific targeting of delayed-type hypersensitivity responsiveness may increase the efficacy of strategies for immuno-intervention against HPV infection in the genital tract.

[1]  G. Orth,et al.  Linkage of regression and malignant conversion of rabbit viral papillomas to MHC class II genes , 1992, Nature.

[2]  E. Butcher Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity , 1991, Cell.

[3]  G. Grindlay,et al.  Studies on vaccination against papillomaviruses: prophylactic and therapeutic vaccination with recombinant structural proteins. , 1991, Virology.

[4]  L. Koutsky Role of epidemiology in defining events that influence transmission and natural history of anogenital papillomavirus infections. , 1991, Journal of the National Cancer Institute.

[5]  I. Frazer,et al.  A "public" T-helper epitope of the E7 transforming protein of human papillomavirus 16 provides cognate help for several E7 B-cell epitopes from cervical cancer-associated human papillomavirus genotypes. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. Lathe,et al.  Immunization against human papillomavirus type 16 tumor cells with recombinant vaccinia viruses expressing E6 and E7. , 1991, Virology.

[7]  T. Mosmann,et al.  Functional diversity of T lymphocytes due to secretion of different cytokine patterns , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  A. Allison,et al.  Adjuvant formulations and their mode of action. , 1990, Seminars in immunology.

[9]  Timothy A. Springer,et al.  Adhesion receptors of the immune system , 1990, Nature.

[10]  C. Griffiths,et al.  The role of adhesion molecules, chemotactic factors, and cytokines in inflammatory and neoplastic skin disease--1990 update. , 1990, The Journal of investigative dermatology.

[11]  P. E. Bishop,et al.  An immunohistological study of spontaneous regression of condylomata acuminata. , 1990, Genitourinary medicine.

[12]  J. Rothbard,et al.  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. , 1990, The Journal of general virology.

[13]  V. Kh,et al.  Human papillomaviruses and cervical carcinoma. , 1989 .

[14]  Krebs Hb Genital human papillomavirus infection. Management strategies. , 1989, Clinical obstetrics and gynecology.

[15]  A. Cunningham,et al.  Role of keratinocytes in human recurrent herpetic lesions. Ability to present herpes simplex virus antigen and act as targets for T lymphocyte cytotoxicity in vitro. , 1989, The Journal of clinical investigation.

[16]  S. Breathnach The Langerhans cell , 1988, The British journal of dermatology.

[17]  M. Jenkins,et al.  Class II MHC-bearing keratinocytes induce antigen-specific unresponsiveness in hapten-specific Th1 clones. , 1988, Journal of immunology.

[18]  M. Campion,et al.  Subpopulations of Langerhans’ cells in cervical neoplasia , 1987 .

[19]  H. Tagami,et al.  Plane warts under spontaneous regression. Immunopathologic study on cellular constituents leading to the inflammatory reaction. , 1986, Archives of dermatology.

[20]  D. Mason,et al.  Langerhans’cells in human cervical epithelium: effects of wart virus infection and intraepithelial neoplasia , 1983, British journal of obstetrics and gynaecology.

[21]  J. Oriel Natural history of genital warts. , 1971, The British journal of venereal diseases.

[22]  A. Kupfer,et al.  T-cell effector functions: mechanisms for delivery of cytotoxicity and help. , 1991, Annual review of cell biology.