Biphasic pattern of thymus regeneration after whole-body irradiation.

Whole-body irradiation of mice with 300 or 400 R causes a precipitous fall in thymus weight, followed by an increase in the mitotic index and an almost complete restoration of thymus mass. This phase is followed by a secondary fall in thymus weight and gradual recovery. This secondary fall can be prevented by intravenous injection of bone marrow or shielding of the hind limbs during irradiation. The hypothesis is proposed that the thymus depends on the migration of cells from the bone marrow to the thymus for the maintenance of its cell population. Bone marrow cells with chromosome markers injected intravenously into normal or lightly irradiated (150 R) animals do not populate the host bone marrow to any significant degree. After whole-body irradiation with heavy doses (400 R), donor cells dominate the marrow. There may be a competition between dividing cells in the bone marrow which regulates proliferation of hemic cells. Bone marrow cells with marker chromosomes do not repopulate the thymus in irradiated animals until long after repopulating the bone marrow. It is possible that these cells have to pass through the marrow or the blood-marrow barrier to acquire characteristics needed for entering the thymus. After whole-body irradiation with 500 R or more, the first phase of regeneration of the thymus, represented by an increase in the mitotic index, does not occur to a significant degree. Apparently cells in the thymus capable of proliferation have been largely eliminated, and restoration of organ mass depends chiefly on seeding from other sources, probably the bone marrow. After whole-body irradiation with 200 R, only the first phase of thymus weight loss and regeneration takes place. Probably bone marrow injury is too small to interfere with the supply of cells repopulating the thymus.