Loss of leukoregulin up-regulation of natural killer but not lymphokine-activated killer lymphocytotoxicity in human papillomavirus 16 DNA-immortalized cervical epithelial cells.
The sensitivity of human cervical epithelial cells immortalized by transfection with human papillomavirus type 16 (HPV16) DNA, to lysis by natural killer (NK) and lymphokine-activated killer (LAK) lymphocytes was evaluated at progressive stages of transformation. Both early- (10-20 wk) and late- (greater than 30 wk) passage HPV16-immortalized cells were resistant to NK lymphocyte cytotoxicity but sensitive to LAK lymphocyte cytotoxicity at lymphocyte-to-cervical cell ratios ranging from 1:1 to 50:1 in a 4-hour 51Cr release assay. Treatment of early-passage HPV16 DNA-immortalized cells with 2.5 U/mL of the NK lymphocytotoxicity-sensitizing lymphokine, leukoregulin, for 1 hour induced modest sensitivity to NK cells (P less than .05) but markedly up-regulated LAK sensitivity twofold to threefold. At the later passages, leukoregulin up-regulation of sensitivity to NK was lost but remained to LAK lymphocytotoxicity. Similarly, an HPV16-positive human cervical carcinoma cell line, QGU, was also resistant to NK lymphocytotoxicity and sensitive to LAK lymphocytotoxicity; leukoregulin failed to confer sensitivity to the NK-resistant QGU tumor cells and increased their sensitivity to LAK lymphocytotoxicity 1.5-fold to twofold. Although the HPV-immortalized cervical cells containing integrated HPV16 DNA were not tumorigenic, they mimicked the response of established HPV16-positive cervical carcinoma cells. HPV16-immortalized cervical epithelial cells provide a useful model for the study of cytokine modulation of dysplastic and neoplastic cervical epithelial cell sensitivity to natural lymphocytotoxicity.
Furbert-Harris
P M
PM
Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892.
Evans
C H
CH
Woodworth
C D
CD
DiPaolo
J A
JA
D002461:Cell Line, Transformed / Q000187:drug effects; D002470:Cell Survival; D002584:Cervix Uteri / Q000473:pathology*; D003602:Cytotoxicity, Immunologic; D004279:DNA, Viral; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000494:pharmacology*; D027383:Papillomaviridae / Q000235:genetics*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000473:pathology
D004279:DNA, Viral; D008222:Lymphokines; C044162:leukoregulin