title: Accumulation of invariant NKT cells with increased IFN-γ production in persistent high-risk HPV-infected high-grade cervical intraepithelial neoplasia.
abstract: BACKGROUND
  Persistent high-risk human papillomavirus (HR-HPV) infection has been implicated in the development of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. Invariant natural killer T (iNKT) cells produce large amounts of cytokines to regulate immune responses. However, the role of iNKT cells in human persistent HPV-infected cervical tissues is unknown.
  
  
  METHODS
  In our study, 201 patients with diagnoses ranging from normal ectocervical tissue to CINIII from June 2010 to May 2012 were enrolled. HPV DNA and HPV types were detected using the hybrid capture-2 HPV DNA test. Flow cytometry was used to investigate iNKT and CD3+ T cell infiltration into cervical tissues. Real-time quantitative reverse transcription-polymerase chain reaction was used to study IFN-γ expression and immunohistochemistry was used to determine CD3+ T cell distribution.
  
  
  RESULTS
  A significant increase in iNKT cells was observed in HPV-positive cervical tissues (p < 0.05), especially in CINII-III (p < 0.01). IFN-γ expression was also increased in HPV-positive cervical tissues (p < 0.05). CD3+ T cells were detected among both epithelium and stromal layers in cervical tissues, and the percentage of CD3+ T cells in HPV-positive cervical tissues was similar to that in HPV-negative cervical tissues (p > 0.05).
  
  
  CONCLUSIONS
  The iNKT cell aggregation in cervical tissues during the progression from HPV infection to CIN indicates that iNKT cells might play an important role in suppressing immunity. IFN-γ expression could also be related to the HPV infection status. Preventing the accumulation or functioning of iNKT cells in cervical tissues may be a viable method to prevent the development of CIN.
  The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2521874671514142.
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. huting4123@163.com.|Laboratory of Cell and Gene Therapy, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. huting4123@163.com.|Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. huting4123@163.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Hu
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. yangpei_cd@sina.com.|Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. yangpei_cd@sina.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. zhuhongmei_hx@sina.com.|Laboratory of Cell and Gene Therapy, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. zhuhongmei_hx@sina.com.|Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. zhuhongmei_hx@sina.com.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. xinlanchen1977@sina.com.|Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. xinlanchen1977@sina.com.|Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. xinlanchen1977@sina.com.
authors.forename: Xinlian
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. xyxie1981@sina.com.|Laboratory of Cell and Gene Therapy, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. xyxie1981@sina.com.|Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. xyxie1981@sina.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. yangmei_cd@sina.com.|Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. yangmei_cd@sina.com.|Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. yangmei_cd@sina.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. sunny630@126.com.|Laboratory of Cell and Gene Therapy, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. sunny630@126.com.|Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. sunny630@126.com.
authors.forename: Shanling
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. Wanghe_cd@126.com.|Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. Wanghe_cd@126.com.|Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, No. 20, Section 3, Renming Nan Road, Chengdu, 610041, China. Wanghe_cd@126.com.
authors.forename: He
authors.initials: H
authors.lastname: Wang
mesh_terms: D000328:Adult; D001706:Biopsy; D017252:CD3 Complex / Q000032:analysis; D002584:Cervix Uteri / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D018655:Lymphocyte Count; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000821:virology; D060787:Neoplasm Grading; D030361:Papillomavirus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: D017252:CD3 Complex; C573415:IFNG protein, human; D012333:RNA, Messenger; D007371:Interferon-gamma