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-negative 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 between them. Inoculation of Lym⁺ cells into the brain caused upregulation of the intracellular MHC mRNA to the same level as after treatment with interferon-gamma, resulting in an increase in cell-surface MHC expression. 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 assay, using 2 groups of untreated and NK-cell-depleted syngeneic mice, showed 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 allogeneic or syngeneic preimmunized mice (immunized with tumor cells), Lym⁺ was rejected, while Lym^- was accepted. When allogeneic mice had received 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 activity than Lym⁺ cells, while in T-cell-depleted mice Lym^- was less tumorigenic than Lym⁺. These results suggest that MHC-positive tumor cells grafted into the brain may be rejected by CTL in an MHC-dependent manner, whereas MHC-negative tumor cells can escape from T-cell-mediated immunosurveillance and grow progressively in the brain, due to absence of intracerebral natural resistance mediated by NK cells.