Reversal of Wasting in Thymectomized Mice by the Injection of Syngeneic Spleen or Thymus Cell Suspensions

Hilgard, Henry R.; Yunis, Edmond J.; Sjodin, Kenneth; Martínez, Carlos A.; Good, Robert A.

doi:10.1038/202668a0

Cited by 23 publications

(15 citation statements)

References 17 publications

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“…Each of these animals has continued to grow normally to the time of writing and is in good condition 1 year after treatment. Reversal of wasting disease was also observed in 3 of 10 thymus cell-injected animals (14).…”

Section: Reversal Of Wasting Disease In Thymectomized Mice By Injectimentioning

confidence: 73%

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Studies on Immunologic Reconstitution of Thymectomized Mice

Yunis

Hilgard

Martínez

et al. 1965

The Journal of Experimental Medicine

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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.

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Section: Reversal Of Wasting Disease In Thymectomized Mice By Injectimentioning

confidence: 73%

“…The animals which recovered from the wasting disease were also restored immunologically, as judged by graft versus host activity in appropriate F1 hybrid animals (14). with hemiallogeneic (A X CsH)F1 spleen cells after onset of the wasting syndrome.…”

Section: Reversal Of Wasting Disease In Thymectomized Mice By Injectimentioning

confidence: 99%

Studies on Immunologic Reconstitution of Thymectomized Mice

Yunis

Hilgard

Martínez

et al. 1965

The Journal of Experimental Medicine

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“…By contrast, 5-20 million spleen or lymph node cells were effective (21,22). Huge numbers of thymus cells (100-300 million) could however, reverse the effects of neonatal thymectomy (23,24) although no comparison was made between spleen and lymph node ceils on the one hand, and thymus cells on the other, with respect to the minimal dose required to achieve an effect. The results reported here indicate that thymus ceils were as good as thoracic duct ceils in enabling neonatally thymectomized mice to respond to sheep erythrocytes when the antigen was given together with the ceils, but 50 million thymus ceUs were inferior to 10 million thoracic duct ceils in preventing wasting disease.…”

Section: Transfer Of Thoracic Duct Cells From Mice Tolerant Of Sheep mentioning

confidence: 99%

Cell to Cell Interaction in the Immune Response

Miller

1968

The Journal of Experimental Medicine

526

130

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An injection of viable thymus or thoracic duct lymphocytes was absolutely essential to enable a normal or near-normal 19S liemolysin-forming cell response in the spleens of neonatally thymectomized mice challenged with sheep erythrocytes. Syngeneic thymus lymphocytes were as effective as thoracic duct lymphocytes in this system and allogeneic or semiallogeneic cells could also reconstitute their hosts. No significant elevation of the response was achieved by giving either bone marrow cells, irradiated thymus or thoracic duct cells, thymus extracts or yeast. Spleen cells from reconstituted mice were exposed to anti-H2 sera directed against either the donor of the thymus or thoracic duct cells, or against the neonatally thymectomized host. Only isoantisera directed against the host could significantly reduce the number of hemolysin-forming cells present in the spleen cell suspensions. It is concluded that these antibody-forming cells are derived, not from the inoculated thymus or thoracic duct lymphocytes, but from the host. Thoracic duct cells from donors specifically immunologically tolerant of sheep erythrocytes had a markedly reduced restorative capacity in neonatally thymectomized recipients challenged with sheep erythrocytes. These results have suggested that there are cell types, in thymus or thoracic duct lymph, with capacities to react specifically with antigen and to induce the differentiation, to antibody-forming cells, of hemolysin-forming cell precursors derived from a separate cell line present in the neonatally thymectomized hosts.

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“…Furthermore, reversal of the postthymectomy wasting syndrome in the mouse can be achieved by the administration of spleen cells (58)(59)(60). Such reconstituted animals also regain the ability to reject allogeneic skin grafts, indicating that the spleen in the mouse can exhibit thymic function as well.…”

Section: Discussionmentioning

confidence: 99%

Cells involved in the immune response: XI. Identification of the antigen-reactive cell as the tolerant cell in the immunologically tolerant rabbit

Abdou¹,

Richter²

1970

Transplantation

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Previous investigations have disclosed that normal allogeneie bone marrow cells can transfer antibody-forming capacity to irradiated rabbits (1-5). On the other hand, "primed" bone marrow (bone marrow obtained from a donor rabbit 24 hr following intravenous administration of the specific antigen) could not transfer antibodyforming capacity to the antigen with which the marrow donor had been immunized, but could transfer immunocompetence to other antigens (3, 4). It was also demonstrated that the antibody-forming cell in the marrow recipient is of host, not donor, origin (5), thus supporting the conclusion that the immunoeompetent cell in the bone marrow is the antigen-reactive cell and that the bone marrow does not contain any antibody-forming cells (4--7). Furthermore, it was demonstrated that antigenreactive cells, isolated by passage of the normal bone marrow cell suspension through an antigen-sensitized glass bead colnmn, followed by elution of retained cells from the column (eluate), could transfer antibody-forming capacity to an irradiated rabbit, but only toward the antigen used to sensitize the glass beads (2). In contrast, the cells which passed through the antigen-sensitized glass bead column (effluent) lost the capacity to transfer immtmoeompetence with respect to the antigen used to sensitize the beads, but not with respect to other non-cross-reacting antigens (2).These findings suggested a means of indentifying which of the cell types concerned with the mediation of the humoral immune response in the rabbit--the antigen-reactive cell or the antibody-forming ceil--is the tolerant cell in the immunologicaily tolerant rabbit. As shown below, it would appear that the antigen-reactive cell is the one which is unresponsive in the latter animal. Materials and MethodsNew Zealand white rabbits were used throughout this study. The antigens used were human serum albumin (HSA) (Ityland Laboratories, Los Angeles, Calif.) and bovine gamma

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Reversal of Wasting in Thymectomized Mice by the Injection of Syngeneic Spleen or Thymus Cell Suspensions

Cited by 23 publications

References 17 publications

Studies on Immunologic Reconstitution of Thymectomized Mice

Studies on Immunologic Reconstitution of Thymectomized Mice

Cell to Cell Interaction in the Immune Response

Cells involved in the immune response: XI. Identification of the antigen-reactive cell as the tolerant cell in the immunologically tolerant rabbit

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