Natural cytotoxicity to human leukemia mediated by mouse non‐t cells

Natural killer (NK) cells cytotoxic for certain syngeneic or allogeneic tumor cells have been described in various species, including mouse, rat and man, as a new type of effector cell. In this paper, we show that mouse NK cells also function in a xenogeneic system. Established human hematopoietic cell lines were used as targets for normal mouse spleen effector cells in a short‐term 51 Cr release assay. Nine malignant lymphoma, two myeloma and four leukemia lines as well as six lympho‐blastoid cell lines of presumed non‐neoplastic origin were tested. Specific and reliable killing was obtained with the T leukemias MOLT‐4, JM, CCRF‐H‐SB‐2 and the myeloid leukemia K 562. Most other lines were sensitive to some degree but their susceptibility and the specificity of the reactions were of doubtful significance. The heterologous cytotoxic reactivity was shown to be caused by the same kind of murine effector cells that mediate NK activity against certain mouse lymphomas by the following criteria: (1) the differences in killing capacity found between spleen cell preparations from genetically “high” or “low” NK‐reactive inbred mouse strains did apply in this heterologous system; (2) cytotoxicity was related in a typical manner to the age of the effector cell donor; (3) spleen cells from T‐deficient nude mice were highly cytotoxic; (4) removal of T cells, B cells and phagocytic cells using standard fractionation procedures did not abrogate the lytic ability of the remaining spleen cell population. Specificity of lysis was assessed using unlabelled cells as competing targets together with labelled target cells. When competitor cells were identical to the target cells, good competition was achieved. Mouse or human cell lines insensitive to lysis by mouse NK cells had no competitive capacity for target cells of either species. Using NK sensitive lines, competition between mouse and human cells was found to be unidirectional with the most sensitive tumors being the best inhibitors. Thus, unlabelled mouse T lymphoma YAC‐1 cells were efficient competitors for lysis of human T leukemia lines. Conversely, susceptible human cells used as competitors did not significantly inhibit killing of YAC‐1 targets. The implications of these findings are discussed.