The self-sustaining capacity of lymphoid cells in the irradiated thymus.

The self-sustaining capacity of thymus lymphoid cells was studied in mice exposed to sublethal doses of X-rays. During exposure various parts of the organism were protected by lead shielding. When the thymus was protected and the rest of the organism exposed to radiation an initial cellular depletion of the thymus not exceeding 70 per cent was followed by a complete cellular regeneration of the organ within 3 weeks. This regeneration was shown to proceed without any cellular support from the bone marrow. When the thymus was included in the radiation field and/or damaged by cortisone treatment resulting in a depopulation exceeding 70 per cent, no or only partial regeneration occurred. The results indicate that the cell population in the thymus of mice can be self-sustaining for at least 3 weeks.

Effect of cortisone and X-irradiation on cellular depletion and regeneration in the thymus of mice: experimental discrimination between thymus lymphocyte precursors in the bone marrow and in the thymus.

The effect of cortisone treatment on the ability of bone marrow cells to repopulate X-irradiated thymus was investigated. In one experimental series, groups of mice were treated first with cortisone and then irradiated with or without bone marrow protection. Mice treated with either cortisone or radiation alone served as controls. During an initial, bone marrow independent phase of thymus regeneration, cortisone had a stronger inhibitory effect on the cellular regeneration of the organ than irradiation. On the other hand, during a subsequent bone marrow dependent phase, thymus regeneration was impaired by radiation exposure but not by cortisone treatment. In another experimental series, irradiated mice were transplanted with bone marrow cells in different numbers from syngeneic donors which had either been treated with cortisone or were left untreated. Twenty days later the cell number was consistently larger in the thymus of animals which has been transplanted with cortisone treated bone marrow than in the animals transplanted with untreated bone marrow. It is concluded that the thymus lymphocyte precursors in the bone marrow and the early precursors of thymocytes in the thymus differ with regard to their sensitivity to cortisone and radiation and, therefore, may represent two distinct cell types.

Dose to the shielded thymic region of irradiated mouse cadavers.

Frozen mouse cadavers were exposed to 220 kV roentgen irradiation with the thymic area covered with a lead plate sized 18 mm X 24 mm X 4 mm oe 18 mm X 12 mm X 4 mm. Lif-Telfon rods were used for dose measurements. With larger plate the mean dose from scattered radiation, in percent of that in the uprotected abdomen, was 12.77 (thymic lobes) and 18.34 (vertebra). With the smaller shield the figures were markedly increased, 16.70 and 23.77, respectively. Since the percentage dose is relatively high, the amount of scattered radiation may have biologic significance.

Cellular repopulation and recovery of the phytogemagglutinine (PHA) responding cell pool in the thymus of sublethally irradiated mice.

Cellular repopulation and recovery of PHA reactivity was investigated in the thymus of mice exposed to 400 R either on the whole body or with one leg protected. In the whole body irradiated cases both the cellular repopulation and the restoration of PHA reactivity in the thymus showed a cyclic pattern: an initial depression and a subsequent first recovery being followed by a secondary cellular depletion and decrease of reactivity before another recovery phase started. The phase of the secondary decrease lasted fo a similar period for both the cell number and reactivity, but was shifted in time and the reduction in reactivity began some 12 days later than that in the cell number. In the leg-shielded animals, the cellular repopulation progressed without cyclic changes, but the recovery of PHA reactivity maintained a cyclic pattern. However, due to a smaller secondary decrease, it was less pronounced than in the whole body irradiated cases. During the aging of mice from 50 to 90 day old, the cell number in the involuting thymus decreased to half of the original. The decrease in the cell population was associated with an about four-fold increase of PHA reactivity. The results were discussed in regard to the origin of the immunoreactive thymic cells. Arguments were presented in favour of the hypothesis that both the reactive and nonreactive cells originate from precursors in common, but require different lengths of time for maturation.

The role of bone marrow in different phases of the cellular repopulation of irradiated mouse thymus.

In one series of experiments, the cellular repopulation of the thymus was investigated in mice exposed first to 200 R on the whole body and, after various intervals, to 700 R with one leg protected or unprotected during the exposure. When no protection was made, the mice were transplanted with syngeneic bone marrow cells in a defined number immediately after irradiation. Repopulation was fastest when the interval between exposures was 5 days, and most delayed when it was 14 days; with a 30 day interval the speed of repopulation was intermediate, and resembled that of a control group exposed to only the second dose. In another experimental series, thymus repopulation was studied after exposure of mice first to 200 R with one leg protected or unprotected and, after an interval of 5, 14 or 30 days, to a second dose of 700 R on the whole body. In all cases, syngeneic bone marrow cells were grafted intravenously after the second irradiation. The thymus repopulation was enhanced by protection of the leg when 14 day interval separated the exposures. In the other cases, no enhancement was noted. The findings were interpreted to indicate that the cellular composition of the thymus and, in particular, the frequency of the proliferating stem cells at the time of the exposure determines thymic repopulation for about two weeks after irradiation. After this period, repopulation is due to new precursors from the bone marrow which seeded the thymus.