H-2I-linked control of immunological resistance to viral leukemogenesis as a response to preleukemic cells

The mechanism of resistance to leukemogenesis by two radiation leukemia virus variants, A-RadLV and D-RadLV, was investigated. Resistance to these viruses is linked toH-2I in both B10.S and C57BL/10 mice. The resistance of virus-infected mice to transplantation of syngeneic, A- or D-RadLV-induced lymphoma cells was similar to their resistance to leukemogenesis by the same viruses. This resistance could be transferred by lymphoid cells from immune donors to normal recipients, and it was specific for RadLV lymphomas. Virus-primed (responder x sensitive)F₁ hybrids rejected only resistant-type parental lymphoma cells. Hence, it appears thatH-2I-linked resistance to RadLV leukemogenesis is regulated byIr genes. Resistant mice immunized by A- or D-RadLV rejected syngeneic lymphoma cells, irrespective of whether they were sensitive or resistant to the RadLV variant used for the induction of the lymphoma cells. It follows that resistant and sensitive type lymphomas are antigenically similar for the effector mechanism, and that theIr genes may be expressed in the sensitization phase of the reaction. In virus-infected mice which are resistant to A- or D-RadLV we were able to demonstrate the presence of preleukemic lymphocytes. Normal mice could be immunized by these preleukemic cells against lymphoma challenge. These data are interpreted to suggest that mice havingH-2I-linked resistance to RadLV infection may be sensitized by their preleukemic cells, and that these preleukemic cells are then arrested in their development as a result of the immune response.