title: Diminished IFN-gamma and IL-10 and elevated Foxp3 mRNA expression in the cervix are associated with CIN 2 or 3.
abstract: Cervical mucosal expression of cytokines involved in mediating cellular immunity is believed to influence the persistence of human papillomavirus (HPV) infection, a necessary prerequisite for the development of cervical intraepithelial neoplasia (CIN). Additionally, regulatory T (Treg) cells are increasingly understood to be important modulators of cellular immunity. Using quantitative RT-PCR, we measured, in cross-sectional design, the cervical mRNA expression of IFN-gamma, IL-10, and IL-12, as well as the Treg transcription factor Forkhead box P3 (Foxp3), in a cohort of young women representing CIN 1, 2, and 3, as well as benign histology. Higher levels of IFN-gamma and IL-10 were significantly (p <or= 0.05) associated with decreased odds of having high-grade cervical disease (CIN 2 or 3) in multivariate logistic regression models. In contrast, higher levels of mucosal Foxp3 expression were associated with increased odds of having CIN 2 or 3 (p = 0.004). In a multivariate model including cervical infection with HPV16 and/or another high-risk HPV type, Foxp3 remained higher in the CIN 2/3 group, but the difference was notably less significant (p = 0.05). These findings support a model in which diminished cellular immunity in the cervical mucosa and mucosal enrichment of Treg cells both contribute to the development of high-grade lesions.
authors.affiliation: Department of Pediatrics, University of California, San Francisco, CA 94143-1374, USA. ottm@peds.ucsf.edu
authors.forename: Mark E
authors.initials: ME
authors.lastname: Scott
authors.forename: Yifei
authors.initials: Y
authors.lastname: Ma
authors.forename: Lili
authors.initials: L
authors.lastname: Kuzmich
authors.forename: Anna-Barbara
authors.initials: AB
authors.lastname: Moscicki
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002584:Cervix Uteri / Q000166:cytology / Q000502:physiology* / Q000503:physiopathology; D003127:Colposcopy; D016207:Cytokines / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000172:deficiency*; D016753:Interleukin-10 / Q000172:deficiency*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016753:Interleukin-10; D012313:RNA; D007371:Interferon-gamma