Tumour cell toxicity for the targets of natural killer cells.

Cells of intraperitoneally transplanted murine leukaemias and sarcomas (L-1210, EL-4, MC-11 and SA-1), were found to be toxic for target cells usually employed for assaying NK cells (K-562, EL-4, YAC-1). The 3H-uridine-ribonuclease method used in our study, in contrast to the 51Cr assay, revealed not only cytotoxicity but also reversible damage to target cell membrane (membrane toxicity). This damage became irreversible if target cells had been pretreated with actinomycin D. To exclude the possible role of an admixture of NK, macrophages and T killer cells, contaminants were removed from suspensions of peritoneal tumour cells from syngeneic mice by adherence to plastic surfaces and separation on Hypaque-Ficoll, and from tumour cells grown in vivo or in vitro and then maintained in allogeneic animals by additional treatment with anti-H-2 sera and complement. The toxic effect depended directly on the dosage of tumour cells. Unlabelled target cells inhibited tumour cell toxicity. The medium used for incubating tumour cells was not toxic for target cells.

[Role of homology in the JC subregion of the H2 complex in the reciprocal suppression of normal killer and tumor cells]. / Rol' gomologii po JC-subraionu H2-kompleksa vo vzaimnoi supressii normal'nykh killerov i opukholevykh kletok.

Attempts have been made to find out 1/whether there is an interaction between normal killers (NK) and tumor cells transplanted in vivo and how both effectors' cytotoxicity against the third participant - NK-sensitive target cells, is affected by the hypothetical interaction; and 2/the implication of H2-complex in the interaction of both the effectors. Use was made of an experimental three-component model in vitro. It included the effector cells of two types. As NK use was made of splenocytes from C57BL/6; CBA; B10; SM; B10.D2; B10.A(3R); B10.A(5R); BALB/C; A/Sn; B10.D2(R107); B.10.D2(R101) mice. Tumor effectors were EL-4 MX-11 (H2b), L-1210 (H2b) and SA-1(H2b) cells transplanted on syngeneic mice. EL-4 cells adapted in culture in vitro were used as standard target cells. Two types of the effector interaction are described. The homology of NK and tumor effector cells in the D-end of H2-complex in the I-C subregion was found to lead to a marked mutual suppression of both the participants with reference to the third component - EL-4 target cells adapted in vitro. The absence of homology in the DC-end of H2-complex provided an opposite effect - summation of cytotoxicity of NK and tumor effector cells against EL-4 target cells. The authors discuss whether the cause of mutual suppression is repaired cytotoxicity (or membrane toxicity) of NK and tumor cells.

[Detection of the cytotoxic effect of tumor cells against the targets of normal killers]. / Obnaruzhenie éffekta tsitotoksichnosti opukholevykh kletok po otnosheniiu k misheniam normal'nykh killerov.

The cells of 2 mouse leukemias (L-1212 and EL-4), the cells of mouse sarcoma (MX-11) and blood lymphocytes from 5 subjects with chronic leukemia were shown to damage the membrane of K-562 and EL-4 cells maintained in vitro. The membrane damage manifested in the rise of the permeability by the pancreatic ribonuclease molecules (m. m. 12,000 d). Experiments with tumor cell suspension fractionation have shown that such permeability cannot be attributed to the admixture of lymphocytes and macrophages to the tumor effector cells. Experiments with cold inhibition have revealed that the damage of the target cell membrane can be produced only by the contact of the tumor cell with the target. It is not related to the deterioration of target metabolism in the presence of a considerable number of tumor cells, or to the accumulation of any toxic products in the culture medium.