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. 1965 Mar 31;121(4):607–632. doi: 10.1084/jem.121.4.607

STUDIES ON IMMUNOLOGIC RECONSTITUTION OF THYMECTOMIZED MICE

Edmond J Yunis 1, Henry R Hilgard 1, Carlos Martinez 1, Robert A Good 1
PMCID: PMC2137986  PMID: 14276780

Abstract

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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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. DALMASSO A. P., MARTINEZ C., SJODIN K., GOOD R. A. STUDIES ON THE ROLE OF THE THYMUS IN IMMUNOBIOLOGY; RECONSTITUTION OF IMMUNOLOGIC CAPACITY IN MICE THYMECTOMIZED AT BIRTH. J Exp Med. 1963 Dec 1;118:1089–1109. doi: 10.1084/jem.118.6.1089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. DE VRIES M. J., VAN PUTTENL, BALNER H., VAN BEKKUMD L'ESIONS SUGG'ERANT UNE R'EACTIVIT'E AUTO-IMMUNE CHEZ DES SOURIS ATTEINTES DE LA "RUNT DISEASE" APR'ES THYMECTOMIE N'EONATALE. Rev Fr Etud Clin Biol. 1964 Apr;9:381–397. [PubMed] [Google Scholar]
  3. EAST J., PARROTT D. M. PREVENTION OF WASTING IN MICE THYMECTOMIZED AT BIRTH AND THEIR SUBSEQUENT REJECTION OF ALLOGENEIC LEUKEMIC CELLS. J Natl Cancer Inst. 1964 Oct;33:673–690. [PubMed] [Google Scholar]
  4. GOOD R. A., DALMASSO A. P., MARTINEZ C., ARCHER O. K., PIERCE J. C., PAPERMASTER B. W. The role of the thymus in development of immunologic capacity in rabbits and mice. J Exp Med. 1962 Nov 1;116:773–796. doi: 10.1084/jem.116.5.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. HESS M. W., COTTIER H., STONER R. D. PRIMARY AND SECONDARY ANTITOXIN RESPONSES IN THYMECTOMIZED MICE. J Immunol. 1963 Sep;91:425–430. doi: 10.2172/4122992. [DOI] [PubMed] [Google Scholar]
  6. HILGARD H. R., YUNIS E. J., SJODIN K., MARTINEZ C., GOOD R. A. REVERSAL OF WASTING IN THYMECTOMIZED MICE BY THE INJECTION OF SYNGENEIC SPLEEN OR THYMUS CELL SUSPENSIONS. Nature. 1964 May 16;202:668–670. doi: 10.1038/202668a0. [DOI] [PubMed] [Google Scholar]
  7. HITZIG W. H., WILLI H. [Hereditary lymphoplasmocytic dysgenesis ("alymphocytosis with agammaglobulinemia")]. Schweiz Med Wochenschr. 1961 Dec 30;91:1625–1633. [PubMed] [Google Scholar]
  8. HUMPHREY J. H., PARROTT D. M., EAST J. STUDIES ON GLOBULIN AND ANTIBODY PRODUCTION IN MICE THYMECTOMIZED AT BIRTH. Immunology. 1964 Jul;7:419–439. [PMC free article] [PubMed] [Google Scholar]
  9. LEVEY R. H., TRAININ N., LAW L. W. EVIDENCE FOR FUNCTION OF THYMIC TISSUE IN DIFFUSION CHAMBERS IMPLANTED IN NEONATALLY THYMECTOMIZED MICE. PRELIMINARY REPORT. J Natl Cancer Inst. 1963 Aug;31:199–217. [PubMed] [Google Scholar]
  10. MARTINEZ C., SMITH J. M., AUST J. B., GOOD R. A. Acquired tolerance to skin homografts in mice of different strains. Proc Soc Exp Biol Med. 1958 Apr;97(4):736–738. doi: 10.3181/00379727-97-23863. [DOI] [PubMed] [Google Scholar]
  11. MARTINEZ C., SMITH J. M., BLAESE M., GOOD R. A. PRODUCTION OF IMMUNOLOGICAL TOLERANCE IN MICE AFTER REPEATED INJECTIONS OF DISRUPTED SPLEEN CELLS. J Exp Med. 1963 Nov 1;118:743–758. doi: 10.1084/jem.118.5.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. MCINTIRE K. R., SELL S., MILLER J. F. PATHOGENESIS OF THE POST-NEONATAL THYMECTOMY WASTING SYNDROME. Nature. 1964 Oct 10;204:151–155. doi: 10.1038/204151a0. [DOI] [PubMed] [Google Scholar]
  13. OSOBA D., MILLER J. F. EVIDENCE FOR A HUMORAL THYMUS FACTOR RESPONSIBLE FOR THE MATURATION OF IMMUNOLOGICAL FACULTY. Nature. 1963 Aug 17;199:653–654. doi: 10.1038/199653a0. [DOI] [PubMed] [Google Scholar]
  14. PETERSON R. D., KELLY W. D., GOOD R. A. ATAXIA-TELANGIECTASIA. ITS ASSOCIATION WITH A DEFECTIVE THYMUS, IMMUNOLOGICAL-DEFICIENCY DISEASE, AND MALIGNANCY. Lancet. 1964 May 30;1(7344):1189–1193. doi: 10.1016/s0140-6736(64)91209-7. [DOI] [PubMed] [Google Scholar]
  15. ROSEN F. S., GITLIN D., JANEWAY C. A. Alymphocytosis, agammaglobulinaemia, homografts, and delayed hypersen sitivity: study of a case. Lancet. 1962 Aug 25;2(7252):380–381. doi: 10.1016/s0140-6736(62)90232-5. [DOI] [PubMed] [Google Scholar]
  16. SJODIN K., DALMASSO A. P., SMITH J. M., MARTINEZ C. THYMECTOMY IN NEWBORN AND ADULT MICE. Transplantation. 1963 Oct;1:521–525. doi: 10.1097/00007890-196301040-00011. [DOI] [PubMed] [Google Scholar]
  17. SVET-MOLDAVSKY G. J., ZINZAR S. N., SPECTOR N. M. DISSOCIATION ON THE IMMUNOLOGICAL COMPETENCE IN NEONATALLY THYMECTOMIZED MICE AND ITS RESTORATION. Nature. 1964 Apr 25;202:353–355. doi: 10.1038/202353a0. [DOI] [PubMed] [Google Scholar]
  18. TAYLOR R. B. IMMUNOLOGICAL COMPETENCE OF THYMUS CELLS AFTER TRANSFER TO THYMECTOMIZED RECIPIENTS. Nature. 1963 Aug 31;199:873–874. doi: 10.1038/199873a0. [DOI] [PubMed] [Google Scholar]
  19. TOBLER R., COTTIER H. Familiäre Lymphopenie mit Agammaglobulinämie und schwerer Moniliasis: die essentielle Lymphocytophthise als besondere Form der frühkindlichen Agammaglobulinamie. Helv Paediatr Acta. 1958 Oct;13(4):313–338. [PubMed] [Google Scholar]
  20. WILSON R., SJODIN K., BEALMEAR M. THE ABSENCE OF WASTING IN THYMECTOMIZED GERMFREE (AXENIC) MICE. Proc Soc Exp Biol Med. 1964 Oct;117:237–239. doi: 10.3181/00379727-117-29545. [DOI] [PubMed] [Google Scholar]
  21. YUNIS E. J., HILGARD H., SJODIN K., MARTINEZ C., GOOD R. A. IMMUNOLOGICAL RECONSTITUTION OF THYMECTOMIZED MICE BY INJECTIONS OF ISOLATED THYMOCYTES. Nature. 1964 Feb 22;201:784–786. doi: 10.1038/201784a0. [DOI] [PubMed] [Google Scholar]

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