title: Immunohistochemical analysis of CD4+ and CD8+ T-cell subsets in high risk human papillomavirus-associated pre-malignant and malignant lesions of the uterine cervix.
abstract: OBJECTIVE
  Humoral and cellular immune responses are likely to play a key role for the clearance or persistence and progression of high risk (HR) HPV-associated cervical lesions. Although there are many studies describing the systemic T-cell responses to HPV16 and 18 proteins, few data are available regarding the cellular mucosal immune responses. We used immunohistochemistry to characterize populations of T-immune cells (CD4+, CD8+, CD45RO+) in HR-HPV-infected precancerous and cancerous lesions of the uterine cervix.
  
  
  METHODS
  Four biopsies from normal cervix, 9 CIN1 which have regressed (rCIN), 5 CIN1 which have progressed (pCIN) to high grade lesions, 13 CIN3 and 11 invasive carcinomas were included. All dysplasias and carcinomas were HR-HPV-positive and low-risk-HPV-negative. They were stained with monoclonal antibodies specific for CD4, CD8 and CD45RO and examined by microscopy.
  
  
  METHODS
  The Kruskal-Wallis test and the Siegel's and Castelan's method were used. RESULTS.: CD4+ cells predominated in regressing CIN1 both within the stroma and the epithelium with the highest CD4+/CD8+ ratio compared with pCIN1, CIN3 and invasive carcinoma. At the exception of CD45RO+ cells, T cells were detected with similar frequencies in both pCIN1 and CIN3. However, in 7 out of 10 CIN3, CD4+ and CD8+ cells were visible as organized lymphoid follicle structure. The CD8+ and CD45RO+ cells far exceeded the CD4+ cells in invasive cancers.
  
  
  CONCLUSIONS
  Density and distribution of immune T cells depend on the malignant potential of HR-HPV lesions. These results suggest that the studied lymphocyte subsets have an important role to fulfil during the natural history of HR-HPV-associated lesions.
authors.affiliation: EA 3181, IFR 133, Université de Franche-Comté, Rue Ambroise Paré, 25000 Besançon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Monnier-Benoit
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mauny
authors.forename: Didier
authors.initials: D
authors.lastname: Riethmuller
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Guerrini
authors.forename: Mihai
authors.initials: M
authors.lastname: Căpîlna
authors.forename: Sophie
authors.initials: S
authors.lastname: Félix
authors.forename: Estelle
authors.initials: E
authors.lastname: Seillès
authors.forename: Christiane
authors.initials: C
authors.lastname: Mougin
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Prétet
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002449:Cell Aggregation / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000276:immunology; D009361:Neoplasm Invasiveness; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000473:pathology / Q000821:virology*
chemical_list: D017493:Leukocyte Common Antigens