title: Regulatory T cells in a spectrum of HPV-induced cervical lesions: cervicitis, cervical intraepithelial neoplasia and squamous cell carcinoma.
abstract: OBJECTIVE
  Thriving of tumors amidst rich immune infiltrates is an unexplained paradox.
  
  
  METHODS
  Immune markers on lymphocytic infiltrates in HPV-positive cervicitis, cervical intraepithelial neoplasia III (CIN III), squamous cell carcinoma (SCC) and normal cervices were characterized immunohistochemically. Regulatory T cells were enumerated and phenotypically characterized using antibodies to FOXP3.
  
  
  RESULTS
  SCCs had higher numbers of CD4 and CD8 cells; infiltrates expressed more CD25, TGFbeta, and IL10 but had significantly lower IL2 compared with cervicitis and CIN III. Expression of CD25 and IL2 correlated well in cervicitis and CIN III but not in SCC. FOXP3 expression was also higher and ratios of CD4/FOXP3 and CD8/FOXP3 were lower in SCC. A fraction of cervicitis, CIN I, CIN II and CIN III had natural (n) regulatory T cells (Tregs); their lesional distribution was predominantly intraepithelial in cervicitis, while in CIN they were also present in the stroma. The proportion of FOXP3(+) CD25(+); FOXP3(+) CD25(-) and TGFbeta(+) CD25(+) in invasive tumors was 17; 19 and 22 respectively.
  
  
  CONCLUSIONS
  Cervical tumors are marked by the presence of an immunoregulatory environment, and harbor equal proportions of 'inactive' n Tregs; activated n Tregs; and Tregs operating via TGFbeta. nTregs in cervicitis and CIN may be a potential marker of persistence.
authors.affiliation: Department of Microbiology, Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.forename: Sreenivas
authors.initials: S
authors.lastname: Adurthi
authors.forename: Sudhir
authors.initials: S
authors.lastname: Krishna
authors.forename: Geetashree
authors.initials: G
authors.lastname: Mukherjee
authors.forename: Uttamchand Deepak
authors.initials: UD
authors.lastname: Bafna
authors.forename: Uma
authors.initials: U
authors.lastname: Devi
authors.forename: Rudrapatna Subramanyam
authors.initials: RS
authors.lastname: Jayshree
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000821:virology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology; D002575:Uterine Cervicitis / Q000276:immunology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000821:virology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta