Proliferative T-cell responses to human papillomavirus type 16 E5 are decreased amongst women with high-grade neoplasia.
Proliferative responses to human papillomavirus type 16 (HPV-16) E5 peptides were determined for short-term cell lines derived from peripheral blood mononuclear cells of 75 women. Cell lines from 16 of the 75 women proliferated in response to stimulation with pooled E5 peptides; this was most common for patients with low-grade squamous cervical intraepithelial lesions (LSIL; 6 of 15 patients, 40%) and less frequent for asymptomatic women with no cervical lesions (4 of 20, 20%), those with high-grade squamous intraepithelial lesions(HSIL; 5 of 33, 15%) and others with cervical cancer (1 of 7, 14%, P = 0.027). Amongst these patients, proliferative responses were exclusive to those that were positive for HPV-16 DNA (12 of 41, 29%; c.f. none of 13 HPV-16 DNA-negative subjects exhibited a proliferative response; P= 0023) and were again most prevalent amongst HPV-16 DNA-positive LSIL (6 of 14, 43%), as compared with HPV-16 DNA-positive HSIL (5 of 23, 22%) or HPV-16 DNA-positive cervical cancer patients (1 of 4, 25%, P > 0.05). In contrast, for asymptomatic women, responsiveness was statistically independent of HPV-16 DNA status, i.e. responsiveness in HPV-16 DNA-positive and DNA-negative subjects was observed in 3 of 15 (20%) and 1 of 5 (20%) cases, respectively (P > 0.05). There were no associations between detection of HPV-16 mRNA and proliferative responses (P> 0.05). These data suggest that HPV-16 E5-specific T-helper activity is depressed amongst women with HSIL lesions.
Department of Infection, Rayne Institute, Guy's Medical and Dental School, London, UK.
D K
DK
Gill
J M
JM
Bible
C
C
Biswas
B
B
Kell
J M
JM
Best
N A
NA
Punchard
J
J
Cason
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000097:blood / Q000276:immunology* / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology*; D030361:Papillomavirus Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014412:Tumor Virus Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000276:immunology* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000097:blood / Q000276:immunology* / Q000821:virology; D000086082:Viroporin Proteins
D009856:Oncogene Proteins, Viral; D010455:Peptides; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins