Bone marrow-derived dendritic cells and the protection against X-ray-induced thymic leukemia in mice. A new interpretation.

About forty years ago, Henry Kaplan and collaborators reported that four weekly X-ray doses of 160 rads each were highly leukemogenic in C57BL mice. A single dose of 350 Rads had a week leukemogenic effect. These authors also demonstrated that lead shielding of the thigh during irradiation prevented the development of leukemia. They reported that intravenous injection of syngeneic bone marrow cells into irradiated mice facilitated the regeneration of the thymus and prevented the development of X-ray-induced tumors. We characterized the thymic Ia+ dendritic cells (DC) with the aid of a fluorescence-activated cell-sorter (FACS). It was found that exposure of mice to a leukemogenic regimen of fractionated X-irradiation treatment led to a gradual decrease in the number of thymic DC. The disappearance of thymic DC and the development of leukemia were prevented by intravenous injection of syngeneic bone marrow or by lead shielding of the femur during irradiation. These results indicated that the fractionated irradiation caused a decline in the number of DC and, as a result, diminution of the natural defense against the developing tumor. Homing of the injected bone marrow DC into the thymus can be connected to the prevention of tumor development. Since leukemogenic T cells produce interleukin-4(IL-4), we tested the effect of the conditioned medium in which YAB-3 cells (tumorigenic Th cells: CD4+, CD8-, Thy-1+) were cultivated. Following injection of the conditioned medium into the mouse footpads, the number of skin Langerhans cells (LC) decreased.(ABSTRACT TRUNCATED AT 250 WORDS)