H-2 associated resistance to leukaemia transplantation: natural killing in vivo.

Natural resistance in vivo was studied by injecting non-immunized mice with leukaemia cells prelabelled with the thymidine analogue 131I-iododeoxyuridine. There was a decrease in the survival of the leukaemia cell inoculum as determined by whole-body gamma counting, and a failure of the leukaemia cells to survive in the spleens of mice which were not H-2 identical with the transplant. H-2-associated resistance could be measured within 24 h of leukemia inoculation and was strongest in the spleen and absent from the liver. Although all strains of mice tested were able to resist H-2 non-identical cells, resistance in irradiated (800--900 R) mice was restricted to certain strains and their F1 hybrids, notably those of the C57BL family. Resistance in both non-irradiated and irradiated mice was not due to classical immunological rejection. Mice with either genetic or induced T-cell deficiency showed full resistance, and circulating preformed antibody could not account for the rejection observed. Treatment with silica or with 89Sr abrogated natural resistance in non-irradiated as well as irradiated animals; these treatments had previously been shown to abolish both bone-marrow graft rejection in irradiated mice and in vitro natural killing. Resistance against leukaemia transplantation in irradiated C57BL mice appeared to depend on Hh-1 (H-2D) incompatibility between the host and the graft, again suggesting that bone-marrow graft rejection, and perhaps natural killer activity, is a subset of a more general paraimmune or non-adaptive rejection mechanism.