1. Immunologic function, growth, and longevity of neonatally thymectomized mice was restored by intraperitoneal administration of 100 to 400 million syngeneic, hemiallogeneic, or ailogeneic thymus cells from newborn or adult donors. Assays of the graft versus host capabilities of spleen cells from the animals restored with allogeneic cells showed that their immunologically competent cells are of donor histocompatibility characteristics. Such animals accepted skin grafts from mice of the cell donor strain, but rejected skin from a third strain.
2. Similar results were obtained when the neonatally thymectomized animals were treated with 10 to 100 million syngeneic, hemiallogeneic, or allogeneic cells from adult spleen.
3. In one strain combination, C3H recipients and A donors, injected thymus or spleen cells apparently attacked host tissues, since the animals died very early of wasting disease. When this combination was reversed, A strain recipients treated with C3H cells were reconstituted immunologically and physiologically.
4. Syngeneic or allogeneic adult spleen, grafted in the newborn period, reconstituted neonatally thymectomized mice, but all experiments involving grafting of newborn spleen failed. Immunogenetic analysis of the host spleen cells from two allogeneic spleen-grafted animals previously thymectomized showed that the reconstitution was entirely of donor histocompatibility characteristics.
5. Postthymectomy wasting disease was reversed by administration of 200 million adult syngeneic spleen or thymus cells. Immunologic recovery was confirmed by graft versus host assays of the spleens of the recovered animals and by application of allogeneic skin grafts. Some of the animals have been under observation for 42 weeks and appear to be normal.
6. The wasting syndrome in neonatally thymectomized mice was also reversed by injection of 200 million hemiallogeneic or allogeneic spleen cells.
7. Thymus grafts did not reverse wasting disease, whether the donors were adult or newborn, of the same strain or a different one.
8. Spleen, lymph node, and Peyer's patches from representative animals of the reconstituted groups were examined and compared with the tissues of untreated neonatally thymectomized mice and intact animals of the same strain. Tissues of normal cellularity and follicular organization were found in some of the reconstituted animals and also in mice with reversed wasting disease. Extreme deficit of the lymphoid tissues was rare in either group.
Thymus cells and bone marrow cells have been shown to interact synergistically in the humoral immune response to sheep erythrocytes. If thymus and bone marrow cells are injected together into heavily X-irradiated hosts, there is approximately a 10-fold increase in the number of antibody-forming cells compared to that seen after injection of either thymus ceils or bone marrow cells alone (1, 2). Attempts to demonstrate such an interaction of thymus ceils and bone marrow ceils in a cellular immune response, the graft-versus-host reaction, have been unsuccessful (3, 4). However, these experiments involving the graft-versus-host reaction were carried out in unirradiated hosts, and therefore are not strictly comparable to the sheep erythrocyte experiments, in which hosts received at least 650 R X-irradiation (1, 2). In the unirradiated host, functional activities of injected donor ceils may be masked by the similar activities of host cells, and in the irradiated host, normal functional activities of donor cells may be altered by the environment which promotes rapid regenerative proliferation. Therefore, in order to carry out experiments on the graft-versus-host reaction which would be comparable to those involving the humoral immune response, we have assessed the capacity of cell suspensions from thymus and bone marrow to produce graft-versus-host splenomega]y in X-irradiated hosts. We report here that cell suspensions of thymus and bone marrow interact synergistically in the production of graft-versus-host sple-*
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