Status of local cellular immunity in interferon-responsive and -nonresponsive human papillomavirus-associated lesions

Sex Transm Dis. Nov-Dec 1996;23(6):475-80. doi: 10.1097/00007435-199611000-00007.

Abstract

Background and objectives: Anogenital warts are caused by human papillomaviruses (HPVs), which should induce cellular immune responses in immunocompetent patients. However, the natural history of these warts shows considerable variation between persons, ranging from spontaneous regression to prolonged persistence. In addition, the efficiency of immunologically based modalities for the therapy of anogenital warts, such as interferon (IFN) treatment, is highly variable.

Methods: Considering that preexisting conditions of the host are important factors in an appropriate immune response, the authors determined the pretreatment status of local cell-mediated immune response to HPV infection by reverse transcription-polymerase chain reaction in patients with condyloma acuminatum, who later received IFN treatment and responded well or poorly to that therapy.

Results and conclusions: The authors found that biopsies from nonresponders were depleted markedly in Langerhans cells, leading to decreases in major histocompatibility complex class II expression and, therefore, to diminished attraction of CD4+ T cells. An inappropriate major histocompatibility complex class I expression also was observed in those nonresponders with decreased CD8+ levels. The mRNA levels of cytokines (interleukin-1a, interleukin-1b, granulocyte-macrophage-colony stimulating factor, tumor necrosis factor that participate in immune responses were low in nonresponders. In contrast, responders demonstrated high macrophage-natural killer cell (CD16-positive) and activated CD4 (IL-2, interferon gamma-positive, TH1 cells) T-cell recruitment against HPV-infected keratinocytes, which is consistent with a delayed-type hypersensitivity-like cellular immune response. Lack of immune response in nonresponders appeared to correlate with high expression levels of the HPV E7 gene. These differences in local cellular immunity might determine the response rate of HPV-infected cells to immunomodulatory therapies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen-Presenting Cells / metabolism
  • CD4-CD8 Ratio
  • Condylomata Acuminata / immunology*
  • Condylomata Acuminata / pathology
  • Condylomata Acuminata / therapy
  • Cytokines / metabolism
  • HLA Antigens / metabolism
  • Humans
  • Immunity, Cellular
  • Interferons / pharmacology*
  • Langerhans Cells / metabolism
  • Male
  • Papillomaviridae / drug effects*
  • Penile Diseases / immunology*
  • Penile Diseases / pathology
  • Penile Diseases / therapy
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Transcription, Genetic / immunology

Substances

  • Cytokines
  • HLA Antigens
  • RNA, Messenger
  • Interferons