Natural killer cell activity in reticulum-cell sarcomas of SJL/J mice. III. Characterization of the effector cells within RCS that mediate NK lysis.

Abstract

AbstractVarious cell depletion techniques were employed to identify the cells responsible for the natural killer (NK) activity against YAC‐1 targets that is present in lymphoid tissues of SJL/J mice bearing transplantable reticulum‐cell sarcomas (RCS). The NK‐activating potential of irradiated RCS cells (X‐RCS) allowed a comparison of three NK‐cell activities in this model system: conventional, induced and RCS‐cell‐mediated cytotoxicity, represented by effector cells derived from lymphoid tissues of normal, X‐RCS‐injected and RCS‐bearing donors, respectively. Both the conventional and induced NK cells were resistant to pretreatment with anti‐la serum and C, whereas RCS‐mediated NK activity was significantly reduced by similar antiserum treatment. The cytotoxicity expressed by both conventional and induced NK cells was moderately radiosensitive, however, 5‐ to 10‐fold higher doses of irradiation were required to effect an equivalent reduction of RCS‐mediated NK activity. To further characterize the effector cells that mediated RCS‐associated NK activity, viable RCS tumor cells were injected into SJL F1 hybrids that either supported (SJL × C57EL/6 and SJL × A.TH) or did not support [SJL × B10.S(7R)] RCS growth. After pretreatment of RCS cell preparations taken from these F1 mice with alloantisera directed against the non‐SJL parental H‐2 haplotype, to remove F1 host cells (F1‐purified RCS), >75% of NK activity was recovered in the RCS‐injected SJL × C57BL/6 and SJL × A.TH F1 hybrids; however, <15% of NK activity was apparent in RCS‐injected SJL × B10.S(7R) F1 recipients. 89Sr treatment of SJL mice abrogated their ability to show increased (induced) NK activity following injection of X‐RCS. In contrast, viable, F1‐purified RCS cells demonstrated both growth and NK activity in 89Sr‐treated SJL mice that was comparable to that seen in normal controls. Treatment of effector cells with three different NK‐reactive antisera (αLy‐11.2, αNK‐1.2 and αasialo‐GM1) effectively depleted conventional and induced NK activities, but had a minimal effect on RCS‐cell‐mediated NK cytotoxicity. These data support the conclusion that RCS tumor cells of SJL/J origin possess NK cytotoxic function and that, by virtue of their pre‐B‐cell characteristics, they may represent a unique class of NK effectors.