In vitro and in vivo correlates of hybrid tumor resistance

Tumorigenicity of 2 sublines, TU1 and TM5, of the C.B6-H-2(dm4) (dm4) mouse tumor, TDM4, was tested in dm4 and F₁ hybrid mice (from crosses of dm4 with a variety of other strains) to determine the genetics of hybrid resistance to these 2 tumor sublines. Resistance to TU1 was associated with at least 3 genes and required heterozygosity in the H-2D region, with secondary effects attributable to H-2K genes and non-H-2 genes. Resistance to TM5, however, did not require H-2D region heterozygosity, whereas H-2K and non-H-2 genes appeared to have significant effects. For evaluation of possible mechanisms for hybrid resistance, 4 assay systems were used. Comparison of natural killer cell activity in dm4 and various hybrid mice revealed no consistent activity against either TU1 or TM5. Little correlation was seen between resistance and generation of strong T-lymphocyte proliferative responses to the sublines. Likewise, cytotoxic T-lymphocyte (CTL) activity, particularly against TU1, was not associated with increased resistance. In contrast, delayed-type hypersensitivity (DTH) was consistently greater in hybrids with increased resistance to either subline. These results suggest a strong association between DTH responsiveness and hybrid resistance. Furthermore, the association, in some hybrids, of CTL activity with resistance to the TM5 subline, but not to TU1, may mean that different sublines of the same tumor can induce different sets of immune responses.