Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1962 Oct 31;116(5):773–796. doi: 10.1084/jem.116.5.773

THE ROLE OF THE THYMUS IN DEVELOPMENT OF IMMUNOLOGIC CAPACITY IN RABBITS AND MICE

Robert A Good 1, Agustin P Dalmasso 1, Carlos Martinez 1, Olga K Archer 1, James C Pierce 1, Ben W Papermaster 1
PMCID: PMC2137569  PMID: 13949053

Abstract

In rabbits, complete thymectomy before the age of 5 days produced immunologic deficiency in the adult animals, as indicated by reduced antibody production to bovine serum albumin and bacteriophage T2. Homotransplantation immunity was unaffected, however. In an inbred strain of mice, complete neonatal thymectomy resulted in complete inability of the 60-day-old animals to form antibody to bacteriophage T2. Inbred mice, completely thymectomized at birth, had a deficient homograft response, indicated by acceptance of skin homografts from strains differing in both the weaker and stronger (H-2) histocompatibility antigens. Tumor transplants (mammary adenocarcinoma) were also successful across the H-2 genetic barrier in mice thymectomized at birth. Neonatal thymectomy also eliminated the Eichwald-Silmser phenomenon, rendering female mice capable of accepting isografts of male skin. Transplantation immunity in mice was also affected by later thymectomy, at 30 days of age, in certain strain combinations involving weak histocompatibility differences. Spleen and lymph node cells from mice thymectomized at birth or at 6 days of age, and sacrificed 2 months later, did not produce a graft versus host reaction in appropriate F1 hybrid recipients, indicating that such cells are immunologically inactive. Neonatal thymectomy of F1 hybrid mice, and in one strain combination thymectomy at 40 days of age, produced animals with inordinate susceptibility to runt disease (homologous disease) following injection of parent strain spleen cells 35 days (neonatal surgery) and 10 days (surgery at 40 days) later. Mice thymectomized at birth also showed growth failure and were short-lived. Studies of newborn mice indicated that they have true lymphocytes only in the thymus, and lack such cells in the spleen, lymph nodes, and gut. In normal mice, adult lymphoid structure develops gradually, beginning during the 1st week of life and continuing for the next month. In contrast, mice thymectomized at birth do not develop mature lymphoid structure: the lymph nodes and spleens tend to be small and poorly organized, and show a quantitative deficiency in lymphoid cells. It is our current working hypothesis that the thymus makes a major contribution toward the centrifugal distribution of lymphoid cells which, in turn, is essential to the full expression of immunologic capacity.

Full Text

The Full Text of this article is available as a PDF (1.8 MB).

Selected References

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

  1. AUERBACH R. Genetic control of thymus lymphoid differentiation. Proc Natl Acad Sci U S A. 1961 Aug;47:1175–1181. doi: 10.1073/pnas.47.8.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BARTH R., COUNCE S., SMITH P., SNELL G. D. Strong and weak histocompatibility gene differences in mice and their role in the rejection of homografts of tumors and skin. Ann Surg. 1956 Aug;144(2):198–204. doi: 10.1097/00000658-195608000-00009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BILLINGHAM R. E., SILVERS W. K. Induction of tolerance of skin isografts from male donors in female mice. Science. 1958 Oct 3;128(3327):780–781. doi: 10.1126/science.128.3327.780. [DOI] [PubMed] [Google Scholar]
  4. Eichwald E. J., Silmser C. R. Skin. Transplant Bull. 1955;2:148–149. [PubMed] [Google Scholar]
  5. FARR R. S. A quantitative immunochemical measure of the primary interaction between I BSA and antibody. J Infect Dis. 1958 Nov-Dec;103(3):239–262. doi: 10.1093/infdis/103.3.239. [DOI] [PubMed] [Google Scholar]
  6. GAFNI J., MICHAELI D., HELLER H. Idiopathic acquired agammaglobulinemia associated with thymoma. Report of two cases and review of the literature. N Engl J Med. 1960 Sep 15;263:536–541. doi: 10.1056/NEJM196009152631103. [DOI] [PubMed] [Google Scholar]
  7. GOOD R. A., MACLEAN L. D., VARCO R. L., ZAK S. J. Thymic tumor and acquired agammaglobulinemia: a clinical and experimental study of the immune response. Surgery. 1956 Dec;40(6):1010–1017. [PubMed] [Google Scholar]
  8. GOOD R. A., VARCO R. L. A clinical and experimental study of agammaglobulinemia. J Lancet. 1955 Jun;75(6):245–271. [PubMed] [Google Scholar]
  9. GROSS L. Effect of thymectomy on development of leukemia in C3H mice inoculated with leukemic passage virus. Proc Soc Exp Biol Med. 1959 Feb;100(2):325–328. doi: 10.3181/00379727-100-24615. [DOI] [PubMed] [Google Scholar]
  10. LAMBIE A. T., BURROWS B. A., SOMMERS S. C. Clinicopathologic conference; refractory anemia, agammaglobulinemia, and mediastinal tumor. Am J Clin Pathol. 1957 Apr;27(4):444–452. doi: 10.1093/ajcp/27.4.444. [DOI] [PubMed] [Google Scholar]
  11. MACLEAN L. D., ZAK S. J., VARCO R. L., GOOD R. A. The role of the thymus in antibody production; an experimental study of the immune response in thymectomized rabbits. Transplant Bull. 1957 Jan;4(1):21–22. [PubMed] [Google Scholar]
  12. MARIANI T., MARTINEZ C., GOOD R. A. Studies of sex-linked histo-incompatibility in inbred mice: role of age and production of immunological tolerance. Int Arch Allergy Appl Immunol. 1960;16:216–232. doi: 10.1159/000229091. [DOI] [PubMed] [Google Scholar]
  13. MARIANI T., MARTINEZ C., SMITH J. M., GOOD R. A. Age factor and induction of immunological tolerance to male skin isografts in female mice subsequent to the neonatal period. Ann N Y Acad Sci. 1960 May 31;87:93–105. doi: 10.1111/j.1749-6632.1960.tb23181.x. [DOI] [PubMed] [Google Scholar]
  14. MARTIN C. M., GORDON R. S., MCCULLOUGH N. B. Acquired hypogammaglobulinemia in an adult; report of a case, with clinical and experimental studies. N Engl J Med. 1956 Mar 8;254(10):449–456. doi: 10.1056/NEJM195603082541002. [DOI] [PubMed] [Google Scholar]
  15. MARTINEZ C., KERSEY J., PAPERMASTER B. W., GOOD R. A. Skin homograft survival in thymectomized mice. Proc Soc Exp Biol Med. 1962 Jan;109:193–196. doi: 10.3181/00379727-109-27149. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. MARTINEZ C., SMITH J. M., AUST J. B., MARIANI T., GOOD R. A. Transfer of acquired tolerance to skin homografts in mice. Proc Soc Exp Biol Med. 1958 Jul;98(3):640–641. doi: 10.3181/00379727-98-24134. [DOI] [PubMed] [Google Scholar]
  18. MILLER J. F. Immunological function of the thymus. Lancet. 1961 Sep 30;2(7205):748–749. doi: 10.1016/s0140-6736(61)90693-6. [DOI] [PubMed] [Google Scholar]
  19. MUELLER A. P., WOLFE H. R., MEYER R. K. Precipitin production in chickens. XXI. Antibody production in bursectomized chickens and in chickens injected with 19-nortestosterone on the fifth day of incubasion. J Immunol. 1960 Aug;85:172–179. [PubMed] [Google Scholar]
  20. OPSTAD A. M. A methyl green-pyronin stain for plasma cells in tissues. Stain Technol. 1959 Sep;34:293–293. [PubMed] [Google Scholar]
  21. PAPERMASTER B. W., BRADLEY S. G., WATSON D. W., GOOD R. A. Antibody-producing capacity of adult chicken spleen cells in newly hatched chicks. J Exp Med. 1962 Jun 1;115:1191–1210. doi: 10.1084/jem.115.6.1191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. PAPERMASTER B. W., FRIEDMAN D. I., GOOD R. A. Relationship of the bursa of Fabricius to immunologic responsiveness and homograft immunity in the chicken. Proc Soc Exp Biol Med. 1962 May;110:62–64. doi: 10.3181/00379727-110-27423. [DOI] [PubMed] [Google Scholar]
  23. PORTER K. A., COOPER E. H. Transformation of adult allogeneic small lymphocytes after transfusion into newborn rats. J Exp Med. 1962 May 1;115:997–1008. doi: 10.1084/jem.115.5.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. PORTER K. A. Runt disease and tolerance in rabbits. Nature. 1960 Mar 12;185:789–790. doi: 10.1038/185789a0. [DOI] [PubMed] [Google Scholar]
  25. RAMOS A. J. Presentation of case. J Am Med Assoc. 1956 Apr 14;160(15):1317–1319. [PubMed] [Google Scholar]
  26. SIMONSEN M., ENGELBRETH-HOLM J., JENSEN E., POULSEN H. A study of the graft-versus-host reaction in transplantation to embryos, F1 hybrids, and irradiated animals. Ann N Y Acad Sci. 1958 Oct 7;73(3):834–841. doi: 10.1111/j.1749-6632.1959.tb40863.x. [DOI] [PubMed] [Google Scholar]
  27. STETSON C. A., Jr, DEMOPOULOS R. Reactions of skin homografts with specific immune sera. Ann N Y Acad Sci. 1958 Oct 7;73(3):687–692. doi: 10.1111/j.1749-6632.1959.tb40845.x. [DOI] [PubMed] [Google Scholar]
  28. STONER R. D., HALE W. M. Antibody production by thymus and Peyer's patches intraocular transplants. J Immunol. 1955 Sep;75(3):203–208. [PubMed] [Google Scholar]
  29. Swift H. F., Wilson A. T., Lancefield R. C. TYPING GROUP A HEMOLYTIC STREPTOCOCCI BY M PRECIPITIN REACTIONS IN CAPILLARY PIPETTES. J Exp Med. 1943 Aug 1;78(2):127–133. doi: 10.1084/jem.78.2.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. THORBECKE G. J., KEUNING F. J. Antibody formation in vitro by haemopoietic organs after subcutaneous and intravenous immunization. J Immunol. 1953 Feb;70(2):129–134. [PubMed] [Google Scholar]
  31. TRENTIN J. J. Tolerance and homologous disease in irradiated mice protected with homologous bone marrow. Ann N Y Acad Sci. 1958 Oct 7;73(3):799–810. doi: 10.1111/j.1749-6632.1959.tb40859.x. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES