Genetic resistance to transplantation of xenogeneic bone marrow in mice of various strains: influence of an interferon inducer and age.

Mice of the C57Bl/6 strain and its hybrids develop at 3-4 weeks of age strong resistance to haemopoietic reconstitution by Lewis rat bone marrow cells (RBMC), whereas mice of other strains show moderate (129/J) or (A/J) such resistance. To test whether interferon (IFN) inducers can boost xenogeneic resistance in these strains, 2-week-old C57Bl/6J and 8-week-old 129/J and A/J mice were injected 4 h after 950 R with the IFN inducer poly I:C and later given various doses of Lewis RBMC. Infant C57Bl/6J mice so injected had significantly fewer numbers of colonies (enhanced resistance) per spleen than did control animals 6 days later. Poly-I:C-injected adult 129/J mice also showed fewer colonies than control mice, whereas poly-I:C-injected and control A/J mice showed similar numbers of spleen colonies. Enhanced resistance induced by poly I:C could be overridden by injecting syngeneic thymocytes with RBMC or by large doses of RBMC alone. Aged and young adult C57Bl/6J mice showed very low numbers of spleen colonies with RBMC inocula up to 20 x 10(6) but resistance breaks at both ages with inocula of 40 x 10(6) RBMC. Young adult and aged A/K mice showed colony confluency with RBMC greater than or equal to 10(6). The results demonstrate that (1) the mechanism of xenogeneic resistance not yet competent in infancy can be driven to functional competence by an IFN inducer in C57Bl/6J mice; (2) resistance can be enhanced in a moderately resistant strain (129/J) by an IFN inducer but not created in a non-resistant strain (A/J); (3) ply-I:C-induced enhancement of resistance can be overridden by giving large numbers of RBMC (+/- syngeneic thymocytes); (4) senescence has no influence on the genetically determined response to marrow xenografts in the strains studied.