Acute rejection of interferon-treated leukemia cells injected into lethally irradiated syngeneic mice

Interferon (IFN) treatment of target cells can alter their susceptibility to natural resistance (NR), evidenced as in vitro 'natural killer' (NK) cell-mediated lysis or as in vivo rapid cell clearance. This paper reports the consequence of direct in vitro treatment with IFN-alpha/beta or IFN-gamma on acute rejection of leukemia cells in lethally irradiated hosts. This type of rejection has the characteristics of NR, although it is specific and genetically regulated. The data were obtained injecting intravenously FLC (FLC-745 and FLC-3C18 clones; H-2d) and EL-4 (H-2b) leukemia lines in lethally irradiated syngeneic mice and evaluating proliferation 4 days later by 125IUdR uptake. Overnight pretreatment with 100 U/ml of IFN-gamma protected tumor cells from NR-induced rejection in mice. This was evident by higher 125IUdR incorporation in spleens of mice inoculated with IFN-gamma pretreated leukemia cells, as compared to that detected in the spleens of hosts injected with untreated cells, in mice with high levels of NR, but not in hosts depressed for NR. Treatment with 1,000 U/ml of IFN-alpha/beta induced protection only of FLC-745 cells, injected in Poly I:C stimulated hosts. On the other hand, a lower 125IUdR uptake after IFN-alpha/beta incubation, as compared with control cells, was evidenced with FLC-745 and EL-4 lines inoculated in mice with normal or depressed NR. The IFN-induced alterations of leukemia cells to in vivo NR susceptibility were not associated with substantial changes of binding ability to NR effectors or of MHC-antigen expression.