[Experimental analysis of intracerebral natural resistance against H-2+ and H-2- lymphomas grafted into the brain]

The authors have investigated intracerebral natural resistance mechanism after tumor transplantation into the brain, by using YAC-1 (Moloney leukemia virus-induced T cell lymphoma of A/Sn mouse origin) and its H-2 negative A. H-2-. It was found that highly immunogenic H-2+ YAC-1 was less tumorigenic than A. H-2- in untreated as well as NK-depleted syngeneic mice. The variant cells were not rejected even if inoculated together with YAC-1 cells into the brain. Furthermore, in T cell-depleted, thymectomized mice YAC-1 was as tumorigenic as A. H-2-. Thus, intracerebral natural resistance was expressed against YAC-1, suggesting that T cells but not NK cells might be involved in the tumor rejection with an MHC-restricted regulation. Contrary to this, A. H-2- cells escaped from the natural resistance of the brain. In vitro cytotoxicity assays showed that in relation to the enhancement of cell surface H-2 antigens, intracerebrally passaged YAC-1 cells decreased and increased the sensitivity to NK- and CTL-mediated lysis, respectively. In contrast, A. H-2- did not alter either susceptibility to cell-mediated lysis or cell surface H-2 expression. In vivo rapid elimination assays revealed that after intravenous or subcutaneous inoculation there was a more efficient abrogation of 125I-iododeoxyuridine (IUdR) labelled YAC-1 cells in normal untreated mice compared to NK-depleted mice. After intracerebral inoculation, however, no difference in remaining radioactivity was observed between untreated and NK-depleted mice. This indicates that selective NK-mediated elimination of tumor cells might occur after intravenous or subcutaneous but not after intracerebral inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)