Correlation of T-helper secretory differentiation and types of antigen-presenting cells in squamous intraepithelial lesions of the uterine cervix

J Pathol. 1998 Mar;184(3):283-90. doi: 10.1002/(SICI)1096-9896(199803)184:3<283::AID-PATH25>3.0.CO;2-K.

Abstract

This study addressed the notion that the progression of cervical cancer is associated with a T-helper 2 (TH2) immunodeviation by analysing cytokine expression in 60 cervical biopsy specimens, spanning the spectrum from normal cervical tissue to high-grade squamous intraepithelial lesions (SILs). The biopsies were analysed by immunohistochemistry for the expression of TH1 [interleukin-2 (IL2), interferon gamma (IFN gamma)] and of TH2-type cytokines (IL4, IL6). Positive cells were usually observed in the subepithelial connective tissue, where most CD4+ cells were also detected. The density of IL2+ cells was significantly lower in high-grade SILs than in normal tissues taken either from the ectocervix or from the transformation zone. In contrast, significantly higher densities of IL4+ cells and, to a lesser degree, IL6+ cells were found in SIL biopsies compared with histologically normal tissues taken from the adjacent ectocervical region. A significantly higher IL4+/CD4+ cell ratio was also found in high-grade SILs (82 per cent) than in normal cervical biopsies taken from the transformation zone of healthy women showing squamous metaplasia (27 per cent). The elevated density of TH2+ cells in SIL biopsies was associated with both the expression of HLA-DR by keratinocytes and a diminished number of intraepithelial Langerhans' cells (CD1a+). In conclusion, the increased TH2+/CD4+ cell ratio in SIL biopsies suggest the presence, during cervical carcinogenesis, of a TH2 immunodeviation that could participate in the immunoescape of preneoplastic cervical keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / immunology*
  • Cervical Intraepithelial Neoplasia / immunology
  • Cytokines / biosynthesis*
  • Disease Progression
  • Female
  • HLA-DR Antigens / analysis
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-2 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Papillomaviridae / classification
  • Papillomaviridae / isolation & purification
  • Precancerous Conditions / immunology*
  • Precancerous Conditions / pathology
  • Precancerous Conditions / virology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology

Substances

  • Cytokines
  • HLA-DR Antigens
  • Interleukin-2
  • Interleukin-4