NATURAL-KILLER AND LECTIN-DEPENDENT CYTOTOXIC ACTIVITIES OF KURLOFF CELLS - TARGET-CELL SELECTIVITY, CONJUGATE FORMATION, AND CA++ DEPENDENCY

Kurloff cells may represent a major component of NK cell activity in t he guinea pig. We have pursued to characterize the mechanism of their action. Using murine target cells, we found Kurloff cell cytotoxicity to be selective for the NK-sensitive YAC-1 target cell, with minimal a ctivity against the NK-resistant P815 target cell. In the presence of PHA, but not ConA, cytotoxicity was markedly augmented against both YA C-1 and P815. While effector-target conjugate formation was observed w ith YAC-1 cells but not P815 cells in control cultures, it was augment ed with both target cell types in cultures with PHA. Pretreatment alon e with PHA was ineffective, however. NK cell activity of Kurloff cells was dependent on extracellular Ca++ and entry of Ca++ into the effect or cells, as demonstrated by abrogation of cytotoxicity when extracell ular Ca++ was chelated with EDTA or EGTA, or following treatment with the Ca++ channel blockers-verapamil and diltiazem. Furthermore, inhibi tion of PKC by H7 resulted in significant reduction of Kurloff cell-me diated NK activity, while pretreatment of effector cells with the PKC activator TPA enhanced NK activity. Kurloff cells could also be stimul ated to produce serine esterases by contact with target cells or treat ment with phorbol ester and ionophore. Finally, a majority of Kurloff cells, identified by the monoclonal antibody 14D1, reacted with the hu man NK cell marker CD56. Taken together, these data suggest that Kurlo ff cells have NK-like characteristics and activity, with target cell s electivity, and that their lytic mechanisms involve influx of extracel lular Ca++, PKC activation and serine esterase production.