High-risk human papilloma virus infection decreases the frequency of dendritic Langerhans' cells in the human female genital tract

Immunology. 2006 Feb;117(2):220-8. doi: 10.1111/j.1365-2567.2005.02282.x.

Abstract

Dendritic cells (DC) are often arranged in planar layers in tissues with high antigenic exposure, such as skin and mucosae. Providing an en face view, this arrangement optimizes in situ analysis regarding morphology (even of individual dendrites), topographic distribution (regular/clustered) and quantification. The few reports on human genital DC usually utilize single markers and conventional sections, restricting immunolabelling only to cell parts sectioned by the cut. To better assess DC in situ, we labelled epithelial sheets, prepared from fresh cervix biopsies, with antibodies to major histocompatibility complex (MHC)-CII, CD1a and Langerin, revealing (with each of these markers) a dense DC network in a planar-like, regular distribution. Using the hybrid capture system to detect the high-risk mucotropic human papilloma virus (HPV) group, 16 positive and five negative women were studied and the results were compared between these groups. DC frequency per area was substantially reduced (to approximately 50% for the three markers) in samples from all HPV-infected patients compared with samples from controls. Unlike HPV(-) samples, Langerin(+) DC in HPV(+) cervix exhibited a highly accentuated dendritic appearance. We believe this to be the first study using these three DC-restricted markers (Langerin, CD1a and MHC-CII) in cervical epithelial sheets from high-risk HPV(+) donors and also the first study to demonstrate the morphological and quantitative changes triggered by high-risk HPV infection. Cervical DC reduction in early, premalignant high-risk HPV infection might represent viral subversion strategies interfering with efficient antigen handling by the immune system's peripheral sentinels, the DC, perhaps hampering appropriate recruitment and subsequent development of effector (cytotoxic) T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsid Proteins / metabolism
  • Cervical Intraepithelial Neoplasia / immunology
  • Cervical Intraepithelial Neoplasia / pathology
  • Cervical Intraepithelial Neoplasia / virology
  • Cervix Uteri / anatomy & histology
  • Cervix Uteri / immunology*
  • Cervix Uteri / virology
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Female
  • HLA-DR Antigens / analysis
  • Humans
  • Immunoenzyme Techniques
  • Langerhans Cells / immunology*
  • Oncogene Proteins, Viral / metabolism
  • Papillomaviridae*
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / pathology
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology

Substances

  • Capsid Proteins
  • HLA-DR Antigens
  • Oncogene Proteins, Viral
  • L1 protein, Human papillomavirus type 16