The Thymus and Recovery of the Sheep Erythrocyte Response in Irradiated Mice

Abstract

The role of the thymus in the recovery of the sheep erythrocyte response after lethal irradiation has been studied in adult CBA mice with the hemolytic plaque technique of Jerne. This immunological parameter is markedly thymus-dependent. 10 wk after irradiation and after antigenic challenge the thymectomized animal has only one-twentieth to one-fortieth the number of plaque-forming cells as does the irradiated animal with intact thymus. The thymus continues to function into the 7th and 8th month of life in this strain. Unlike the drug-tolerant animal, the incompetent irradiated thymectomized mouse retains base line plaques (plaques without antigenic stimulation). Thymectomy 18 days after irradiation is as effective as prior thymectomy in preventing recovery of the sheep cell response. Thymectomized animals receiving grafts of isogenic neonatal thymus (placed beneath the kidney capsule) 1 day, 1 wk, or 2 wk after irradiation are somewhat more responsive at 10 wk than intact animals. Grafts in place for 1 or 2 wk after irradiation and then removed result in one-fifth the recovery of grafts in place the entire time, while only slight restoration is obtained from grafts in place for the final 3 wk of the experiment. The results indicate that the thymus is not required for the 18 days after irradiation, that a period of at least 3 wk residence is required for complete restoration, and that the thymus itself is somewhat radiation-sensitive. Allogeneic thymus grafts failed to restore the hemolysin response of irradiated thymectomized animals.

Cellular Differentiation of the Immune System of Mice

“…In such mice new ARC were formed in sites other than the thymus. However, the kinetics of splenic ASU formation did not differ greatly from those we described in nonthymec-tomized marrow chimeras, and others described in chimeras with thymuses implanted under the kidney capsule (20). It is possible that a humoral factor elaborated by the thymus controlled differentiation of marrow cells into ARC (17).…”

Allogeneic Thymus Grafts and the Restoration of Immune Function in Irradiated Thymectomized Mice

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Experimental Design.--The details were similar to those in previous publications (1,6,7).Adtflt mice (female, 8-10 wk old) were thymectomized, lethally irradiated (875 R, 280 kv, 1.4 mm Cu, 67 R/min), and injected intravenously with 4-5 million marrow cells obtained from the femurs of animals of the same strain and sex. Thymectomy was done within the week prior to irradiation, and marrow grafting in the 4 hr after irradiation.

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Recovery of Immune Responsiveness in Lethally-irradiated Mice Protected with Syngeneic Marrow Cells

“…Furthermore, thymic weight is rarely if ever fully regained in such animals ). Aisenberg and Davis (1968) have shown that thymectomy 18 days after irradiation is as effective as prior thymectomy in preventing marrow-derived immunological recovery. It would, therefore, appear likely that at least part of the time required for the production of antigen-reactive cells in the present recovery studies may be attributed to radiation damage to the primary (inductive) function of the thymus.…”