Langerhans’ Cells in Squamous Metaplasia of the Human Uterine Cervix

Girolamo, Wanda Di; Goñi, José Luis Olcoz; Laguens, Rubén P.

doi:10.1159/000299006

Cited by 8 publications

(5 citation statements)

References 7 publications

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“…We also noted a significant decrease in the density of S100-positive Langerhans' cells in metaplastic epithelium compared with normal exocervical tissue. The reduction of Langerhans' cells in immature metaplasia has already been reported [30] and it has been suggested that the presence of glandular columnar cells provides some kind of negative chemotactic stimulus which prevents migration of Langerhans' cells into metaplastic epithelium [30]. The density of Langerhans' cells detected by anti-S100 antibody in the present study was similar to that previously reported with other antibodies, such as anti-CDla, in normal and pathological cervical tissues [51 ].…”

Section: Discussionsupporting

confidence: 90%

Inverse modulation of intraepithelial Langerhans' cells and stromal macrophage/dendrocyte populations in human papillomavirus-associated squamous intraepithelial lesions of the cervix

Al-Saleh

Delvenne

Arrese

et al. 1995

Vichows Archiv A Pathol Anat

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Ninety-four cervical biopsies from normal tissue to high-grade squamous intraepithelial lesion (SILs) were examined for the presence of intraepithelial Langerhans' cells and subpopulations of stromal macrophages/dendrocytes by immunohistochemistry using anti-S100, -L1, -CD68 and -factor XIIIa antibodies. Human papillomavirus (HPV) detection was performed in all cases by using first a mixture of DNA probes for 14 HPV types commonly found in anogenital biopsies at low stringency conditions (Tm -40 degrees C) and by reanalyzing the tissues at high stringency (Tm -10 degrees C) with HPV 6/11, 16/18 and 31/33/35 biotinylated probe cocktails and individual digoxigenin-labelled probes. SILs and metaplastic tissues were significantly associated with a depletion of S100-positive intraepithelial Langerhans' cells when compared with normal epithelium. In contrast, there was a significant increase in L1-positive stromal macrophages in SIL biopsies compared with normal or metaplastic cervix. A significantly higher density of CD68-positive macrophages was also observed in high-grade SILs compared with normal or metaplastic biopsies and with low-grade SILs. The density of factor XIIIa-positive dendrocytes was found to be higher in SILs compared with metaplastic tissues and in high-grade SILs when compared with normal cervical biopsies. No specific relationship was found between the densities of these cells and the HPV type detected in SILs separated into low grade and high grade. The significance of this inverse modulation of intraepithelial Langerhans' cells and stromal macrophages/dendrocytes in normal and SIL biopsies is discussed in relation to HPV infection and malignant transformation.

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Section: Discussionsupporting

confidence: 90%

Inverse modulation of intraepithelial Langerhans' cells and stromal macrophage/dendrocyte populations in human papillomavirus-associated squamous intraepithelial lesions of the cervix

Al-Saleh

Delvenne

Arrese

et al. 1995

Vichows Archiv A Pathol Anat

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“…41 The anatomical localization of the immune response has also been shown to be an important factor in the TH1/TH2 decision. 42 This is emphasized by the observation, in this study as well as in previous reports, 35,43 of a decreased density of Langerhans' cells in normal cervical tissues showing squamous metaplasia, compared with ectocervical epithelium. It has been suggested that the presence of glandular columnar cells provides some kind of negative chemotactic stimulus which prevents migration of Langerhans' cells into metaplastic epithelium.…”

Section: Discussionsupporting

confidence: 76%

“…It has been suggested that the presence of glandular columnar cells provides some kind of negative chemotactic stimulus which prevents migration of Langerhans' cells into metaplastic epithelium. 43 Another possibility is that there is a decreased production of chemoattractant molecules for Langerhans' cells in the metaplastic epithelium compared with the ectocervical squamous mucosa. The transformation zone of the cervix, where squamous metaplasia occurs, might thus be at greater risk of developing SILs not only because of mechanical factors allowing an easier entry of HPV particles into the basal cell of the metaplastic epithelium, but perhaps also because of the immunological status of this region which is already characterized, in the absence of HPV infection, by a reduced number of Langerhans' cells which have a professional APC function.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1998

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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 (IFNγ)] 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. © 1998 John Wiley & Sons, Ltd.

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“…Previous studies have shown a diminished density of Langerhans cells (LCs) in the transformation zone of the cervix 5,47,48 and in most cervical SILs 49,50 compared with the normal squamous mucosa. Qualitative alterations of LCs have also been reported in SILs.…”

Section: Discussionmentioning

confidence: 99%

Colonization of in Vitro-Formed Cervical Human Papillomavirus-Associated (Pre)Neoplastic Lesions with Dendritic Cells

Hubert

Brûle

Giannini

et al. 1999

The American Journal of Pathology

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The purpose of this study was to investigate the ability of CD1a+ Langerhans/dendritic cells (LCs/DCs) to infiltrate human papillomavirus (HPV)-associated (pre)neoplastic lesions of the uterine cervix. Migration of LCs/DCs in the presence of keratinocytes derived from normal cervix and HPV-transformed cell lines was evaluated in Boyden chambers and in organotypic cultures and correlated with granulocyte/macrophage colony-stimulating factor (GM-CSF) production by the cells, as determined by ELISA. Conditioned media of HPV-transformed keratinocytes contained lower amounts of GM-CSF and induced a decreased motile response of LCs/DCs in the Boyden chamber assay compared with those of normal cervical keratinocytes. The migration of LCs/DCs in the presence of conditioned media from normal keratinocytes could be blocked by an anti-GM-CSF antibody, and the migration of LCs/DCs in the presence of conditioned media from HPV-transformed keratinocytes could be increased by supplementing the media with recombinant GM-CSF. GM-CSF was also a potent factor in enhancing the colonization of LCs/DCs into organotypic cultures of HPV-transformed keratinocytes, as the infiltration of LCs/DCs in the in vitro-formed (pre)neoplastic epithelium was minimal under basal conditions and dramatically increased after the addition of GM-CSF to the cultures. These results suggest that GM-CSF could play an important role in the recruitment of LCs/DCs into the HPV-transformed (pre)neoplastic cervical epithelium and be useful as a new immunotherapeutic approach for cervical (pre)cancers.

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Langerhans’ Cells in Squamous Metaplasia of the Human Uterine Cervix

Cited by 8 publications

References 7 publications

Inverse modulation of intraepithelial Langerhans' cells and stromal macrophage/dendrocyte populations in human papillomavirus-associated squamous intraepithelial lesions of the cervix

Inverse modulation of intraepithelial Langerhans' cells and stromal macrophage/dendrocyte populations in human papillomavirus-associated squamous intraepithelial lesions of the cervix

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

Colonization of in Vitro-Formed Cervical Human Papillomavirus-Associated (Pre)Neoplastic Lesions with Dendritic Cells

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