GUINEA-PIG KURLOFF (NK-LIKE) CELLS MEDIATE TNF-DEPENDENT CYTOTOXIC ACTIVITY - ANALOGY WITH NC EFFECTOR-CELLS

Kurloff cells are mononuclear cells possessing a large cytoplasmic inc lusion body specific to the guinea pig. In this report, we present str ong evidence that Kurloff cells can mediate NC activity against tumor cells in addition to their previously reported NK activity. Using an 1 8 h Cr-51-release assay we have shown that Kurloff cells were highly e ffective in killing the TNF-sensitive WEHI 164 target cell line. Lower but significant cytotoxic activity was also observed after only 4 h. However, our results suggest a different mechanism of lysis in the 4 h and 18 h assay. Lysis of WEHI 164 target cells by Kurloff cells in th e 4 h assay could be strongly increased in the presence of TPA alone o r in combination with ionomycin whereas ionomycin alone was uneffectiv e. In contrast, stimulation of Kurloff cells for 18 h with ionomycin a lone or in combination with TPA could induce the release of TNF-like f actor(s) as observed by the TNF bioassay using L-929 TNF-sensitive tar get cells. Release of TNF-like factor(s) could also be induced by stim ulation with WEHI 164 target cells. Supernatants of Kurloff cells stim ulated for 18 h with TPA + ionomycin were also highly cytotoxic agains t WEHI 164 target cells, but not against the TNF-resistant P815 target cell line. Pretreatment of these supernatants with anti-murine TNF al pha antibodies could almost completely inhibit their cytotoxic activit y against WEHI 164 target cells. In contrast, supernatants of Kurloff cells stimulated for only 4 h did not show any TNF-like activity again st the L-929 target cell line and were not cytotoxic against WEHI 164 target cells even after 18 h. Taken together, these results suggest th at Kurloff cells can mediate NC activity against tumor cells addition to their previously reported NK activity. By using multiple lytic path ways, these cells may play a crucial role in anti-tumor surveillance a nd defenses.