NATURAL-RESISTANCE AGAINST TUMORS GRAFTED INTO THE BRAIN IN ASSOCIATION WITH HISTOCOMPATIBILITY-CLASS-I-ANTIGEN EXPRESSION

The role of MHC-class-I-antigen expression in intracerebral anti-tumor natural resistance was examined using MHC-positive Lym(+) and MHC-neg ative Lym(-) lymphoma cell lines. Lym(+) was sensitive to MHC-class-I- restricted CTL-mediated lysis, while lym(-) was resistant. Both lines were susceptible to NK-cell-mediated lysis. There was no difference in in vitro growth rate or in vivo intraperitoneal tumorigenicity betwee n them. Inoculation of Lym(+) cells into the brain caused upregulation of the intracellular MHC mRNA to the same level as after treatment wi th interferon-gamma, resulting in an increase in cell-surface MHC expr ession. Although inoculated Lym(-) cells also underwent an increase in cytosolic MHC mRNA, the cell-surface MHC expression remained negative . Immunoprecipitation revealed that the terminal glycosylation did not occur normally in Lym(-). An in vivo intracerebral tumorigenicity ass ay, using 2 groups of untreated and NK-cell-depleted syngeneic mice, s howed that Lym(+) was less tumorigenic than Lym(-). In T-cell-depleted mice, however, no difference was detected between them. In addition, when Lym(+) and Lym(-) cells were inoculated into the brain of allogen eic or syngeneic preimmunized mice (immunized with tumor cells), Lym() was rejected, while Lym(-) was accepted. When allogeneic mice had re ceived treatment for T-cell depletion before intracerebral inoculation , no rejection was observed in Lym(+). On the other hand, Lym(-) cells , when injected i.p. into NK-depleted mice, had greater killing activi ty than Lym(+) cells, while in T-cell-depleted mice Lym(-) was less tu morigenic than Lym(+). These results suggest that MHC-positive tumor c ells grafted into the brain may be rejected by CTL in an MHC dependent manner, whereas MHC-negative tumor cells can escape from T-cell-media ted immunosurveillance and grow progressively in the brain, due to abs ence of intracerebral natural resistance mediated by NK cells. (C) 199 6 Wiley-Liss, Inc.