Thymic epithelium is programmed to induce preleukemic changes in retrovirus expression and thymocyte differentiation in leukemia susceptible mice: Studies on bone marrow and thymic chimeras

In the leukemia-prone AKR thymus, ecotropic and xenotropic-related viruses are expressed that generate leukemogenic recombinant viruses before the onset of leukemia. We have shown previously that (AKR x NZB)F₁ hybrid mice do not develop leukemia because they severely restrict the expression of these retroviruses in their thymuses. The thymic microenvironment of the (AKR x NZB)F₁ mice appeared to be of particular importance in determining this restriction, which was specified by an NZB-derived genetic influence. In the present study we analyze reciprocal thymus graft and irradiation bone marrow chimeras to establish that this influence is exerted by thymic reticuloepithelial cells. Prospective studies with thymic epithelial grafts from young mice show that the AKR thymic epithelium can simultaneously induce the amplified expression of retroviral genes, and changes in patterns of thymocyte differentiation that precede the development of leukemia, whereas the (AKR x NZB)F₁ thymic epithelium is deficient in this regard.