Cytotoxic Effector Mechanism and Genetic Control of Non-immunized Hybrid Resistance to Mouse T Cell Lymphoma Transplanted Outside and Inside the Brain

Abstract

A Moloney virus-induced T cell lymphoma, YAC-1, derived from A/Sn (H-2a) inbred mouse origin, was tested for hybrid resistance (HyR) after subcutaneous (s.c.) or intracerebral (i.e.) tumor cell inoculation into syngeneic and semi-syngeneic mice. The F1 hybrids (H-2a/b) between A/Sn and C57BL/6 mice more strongly resisted the s.c. inoculation of 106 and 5 × 105 cells than did syngeneic recipients. In contrast, no HyR to the i.e. inoculation of 104 and 103 cells was seen in the F1 hybrid mice. Natural killer (NK) cell activity was much higher in F1 hybrids than in syngeneic mice. 125I-iododeoxyuridine-labeled YAC-1 cells were more efficiently eliminated from the highly resistant F1 hybrids than from the parental strain in both 4 and 18 hour in vivo rejection assays via intravenous (i.v.) and s.c. injection, respectively. The remaining radioactivity of the brain, however, did not differ between these mice. Thus, there was a correlation between the in vivo resistance of F1 hybrid mice to challenge s.c. inoculation of parental tumors and their expression of lymphocyte-mediated natural cytotoxicity in vitro against those tumors. T cell depletion by thymectomy followed by irradiation and fetal liver reconstitution did not abrogate the s.c. HyR against YAC-1, whereas NK cell depletion by i.v. administration of anti-asialo-GMl antibodies resulted in the disappearance of the resistance. Furthermore, genotypic study segregating (A/Sn × C57BL/ 6)F1 × A/Sn backcross mice indicated that the s.c. HyR might be attributable primarily to heterozygosity within the H-2 complex. Taken together, it was suggested that HyR to an NK cell-sensitive YAC-1 is mediated by an NK cell-dependent cytotoxic effector mechanism with H-2-linked genetic control against s.c. tumor grafts, while such an NK cell-mediated natural resistance does not operate in the brain. © 1990, The Japan Neurosurgical Society. All rights reserved.