title: High-risk human papilloma virus infection decreases the frequency of dendritic Langerhans' cells in the human female genital tract.
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.
authors.affiliation: Department of Experimental Pathology, CINVESTAV-IPN, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Jimenez-Flores
authors.forename: Rene
authors.initials: R
authors.lastname: Mendez-Cruz
authors.forename: Jorge
authors.initials: J
authors.lastname: Ojeda-Ortiz
authors.forename: Rebeca
authors.initials: R
authors.lastname: Muñoz-Molina
authors.forename: Oscar
authors.initials: O
authors.lastname: Balderas-Carrillo
authors.forename: Maria
authors.initials: M
authors.lastname: de la Luz Diaz-Soberanes
authors.forename: Serge
authors.initials: S
authors.lastname: Lebecque
authors.forename: Sem
authors.initials: S
authors.lastname: Saeland
authors.forename: Adrian
authors.initials: A
authors.lastname: Daneri-Navarro
authors.forename: Alejandro
authors.initials: A
authors.lastname: Garcia-Carranca
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Ullrich
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Flores-Romo
mesh_terms: D036022:Capsid Proteins / Q000378:metabolism; D002584:Cervix Uteri / Q000033:anatomy & histology / Q000276:immunology* / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D007801:Langerhans Cells / Q000276:immunology*; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D036022:Capsid Proteins; D006684:HLA-DR Antigens; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16