DIFFERENT SUSCEPTIBILITY OF CERVICAL KERATINOCYTES CONTAINING HUMAN PAPILLOMAVIRUS TO CELL-MEDIATED CYTOTOXICITY

Objective. To detect the factors responsible for the susceptibility of cervical keratinocytes infected with human papillomavirus (HPV) to no n-specific lysis mediated by natural killer (NK) and lymphokine activa ted killer (LAK) cells. Materials and Methods. Five cervical keratinoc yte lines: CaSki, SiHa, HeLa (representing high grade squamous intraep ithelial lesion [HSIL]), W12 (representing low grade squamous intraepi thelial lesion [LSIL]) and NCx, (normal cervix) were used as target ce lls in the four-hour lactate dehydrogenase (LDH) release cytotoxicity assay. The effector cells were NK and LAK. The modulatory effects of i nterferon gamma (IFN gamma) and tumor necrosis factor a (TNF(a)lpha) p retreatment of keratinocytes were investigated by adding IFN gamma, or TNF alpha into the flasks of target cells 48 hours before the cytotox icity assays. The blocking effects of anti-intercellular adhesion mole cule-1 (ICAM-1) and anti-lymphocyte function-associated antigen-1 (LFA -1) monoclonal antibodies (Mabs) were also studied. Results. All the 5 cervical keratinocytes were susceptible to LAK, but not to NK. The se nsitivity varied among the cell lines. LAK had better killing effects on HSIL than on LSIL. Pretreatment of target cells with IFN gamma and TNF alpha increased the killing mediated by LAK, but had little effect on NK activity. Anti-ICAM-1 and anti-LFA-1 Mabs inhibited LAK-mediate d cytotoxicity. Conclusions. All the HPV infected keratinocytes used i n the experiments are NK-resistant and LAK-sensitive cells. IL-2, IFN gamma and TNF alpha play some critical roles in the regulation of the susceptibility of cervical keratinocytes, especially HSIL to LAK-media ted cytotoxicity in vitro.