[Experimental analysis of anti-tumor cytotoxic mechanism for hybrid resistance to mouse neuroblastoma].

A spontaneous neuroblastoma (NB-85, H-2a/a) was tested for hybrid resistance (HyR) after subcutaneous (s.c.) inoculation into syngeneic and semisyngeneic mice. The hybrids (F1) (H-2a/b) between A/Sn and Leaden mice and the F1 between A/Sn X C57BL/6 mice were more resistant to the s.c. inocula of 10(6) to 5 X 10(5) cells than syngeneic recipients. Thymectomy, followed by irradiation and fetal liver reconstitution, abrogated the HyR against NB-85, whereas intravenous (i.v.) administration of anti-asialo-GM1 antibodies had no influence on the resistance. Surface phenotypic analysis revealed that NB-85 expressed H-2 Kk (-), Dd (+) and beta 2-microglobulin (-), showing a dissociation of the cell surface. Anti-H-2a-specific cytotoxic T lymphocytes exhibited a significant lytic activity against NB-85, while NB-85 was highly refractory to natural killer cell (NK)-mediated lysis. In vivo NK-mediated rejection assays showed that 125I-iododeoxyuridine (IUdR) labeled NB-85 cells were not eliminated more efficiently from the highly resistant F1 hybrids than from the parental strain. Furthermore, genotypic study with segregating (A/Sn X Leaden) F1 X A/Sn backcross mice showed that the HyR was attributable primarily to heterozygosity within the H-2 complex. Taken together, it was suggested that the HyR to an NK-resistant mouse NB-85 neuroblastoma might involve a T cell-dependent immunosurveillance with H-2 genetic control.