Studies on the role of the thymus in immunobiology. Reconstitution of immunologic capacity in mice thymectomized at birth

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.

Section: Discussionsupporting

confidence: 55%

mentioning

confidence: 99%

Studies on Immunologic Reconstitution of Thymectomized Mice

Yunis

Hilgard

Martínez

et al. 1965

“…The immunologic deficiency produced by neonatal thymectomy, including prolonged allograft rejection time and lessened antibody responses are restored in part by thymus grafts (16,17), by thymic cells, (18,19), perhaps by thymic extracts (20)(21)(22), and by thymic tumors (23). It was, therefore, of interest to examine the effects of thymus grafts on the in vitro reactions of spleen cells of thymectomized-reconstituted mice.…”

Section: Reconstitution Of In Vitro Responsiveness By Thymus Graftsmentioning

confidence: 99%

Cellular Recognition in Vitro by Mouse Lymphocytes

Takiguchi

Adler

Smith

1971

The thymus is influential in establishing and maintaining elements of immune function throughout life (1, 2) and appears to be required for elicitation of delayed hypersensitivity reactions, for effective rejection of allografts (3, 4), for resistance to tumor induction (5, 6), and for response to certain classes of antigens (7,8). The objective of the studies to be reported here was to examine further the role of the thymus in cellular recognition. The susceptibility of whole and albumin gradient-separated subpopulations of cells taken from mice thymectomized at birth to stimulation in vitro by alloantigens and P H A was assayed. The capacity of thymus grafts of differing origins to restore cellular reactivity was also explored. These studies confirm that the thymus is required for normal levels of responsiveness of lymphoid cells to primary stimulation in vitro by alloantigens and PHA. Materials and MethodsExperimental Animals.--Mice of the inbred strains, C57BL/6J, A/J, BALB/c, DBA/2, and CBA/J, and the F~ hybrids of these strains, were derived from inbred stocks maintained in this laboratory or purchased directly from the Jackson Laboratories, Bar Harbor, Maine.Neonatal Thymectomy and Thymus Grafting Proceclure.--Thymectomy was performed within 24 hr of birth by the method described by Sjodin et al. (9). Macroscopic examination when the animals were sacrificed for an experiment verified the success of thymectomy.The thymus graft procedure was a modification of that of Metcalf et al. (10) in which a polyethylene trocar containing one lobe of newborn thymus tissue was inserted under the left kidney capsule under direct vision. The trocar was approximately the size of an 18 gauge needle and was mounted on a syringe containing 0.5 ml of air.

“…Peyer's patches were cut with scissors from the intestine and suspensions were prepared in glass homogenizers using a standard technique (7,8). Since the patches were usually contaminated with intestinal contents, the fragments were repeatedly washed before preparation of the cell suspension, and all the procedure was performed using Ringer's solution with the addition of 100 units of penicillin and 0.1 mg streptomycin/ml.…”

Section: Methodsmentioning

confidence: 99%

“…This evidence indicated that humoral inducing and/or expanding functions of thymus or thymomas mediate the restoration of the thymectomized hosts. Comparable results were obtained with free thymus grafts, and although restoration was mediated mainly by host-type cells, a thymus-derived cell population could be detected (6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Studies on Thymus Function

Stutman

Yunis

Good

1970

The presence of the thymus in mice is essential for proper development, maintenance, and function of the lymphoid system (1, 2). Thymic function results from the interaction of peculiar cellular migration patterns to and from the thymus (3-10) and from the inductive or expanding capabilities of thymic stroma that include humoral factors (11,12).In previous studies, we have shown that nonlymphoid thymomas induced restoration of immunological functions in neonatally thymectomized mice (13). When thymomas were grafted into allogeneic hosts, immunological restoration was mediated by lymphoid cells of host type (14). Thymomas and normal thymus were also capable of inducing restoration when enclosed in truly cell-impenetrable diffusion chambers (12). This evidence indicated that humoral inducing and/or expanding functions of thymus or thymomas mediate the restoration of the thymectomized hosts. Comparable results were obtained with free thymus grafts, and although restoration was mediated mainly by host-type cells, a thymus-derived cell population could be detected (6-10).When the treatment of neonatally thymectomized hosts with thymomas or thymus grafts was delayed after neonatal thymectomy, a decrease in the restorative influence was observed (15). These results indicate that a population of cells in the thymectomized hosts capable of responding to the action of thymus or thymomas decreased progressively with time after neonatal thymectomy in absence of thymic function, when the mice were nursed in a conventional environment (15). This decrease was interpreted as a result of physiological attrition of cells differentiated prior to thymus extirpation (15).