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. 1970 Sep 1;132(3):583–600. doi: 10.1084/jem.132.3.583

STUDIES ON THYMUS FUNCTION

I. COOPERATIVE EFFECT OF THYMIC FUNCTION AND LYMPHOHEMOPOIETIC CELLS IN RESTORATION OF NEONATALLY THYMECTOMIZED MICE

Osias Stutman 1, Edmond J Yunis 1, Robert A Good 1
PMCID: PMC2138805  PMID: 4943928

Abstract

Immunological restoration of 45-day old, neonatally thymectomized C3Hf mice by treatment with humoral thymic function (thymoma grafts, thymus or thymoma in diffusion chambers) ranges from 0 to 12% and is difficult to acheive. When small numbers (5–20 x 106) of young adult lymphohemopoietic cells, ineffective by themselves, are given in association with humoral thymic function, a cooperative effect is observed and restoration ranges from 30 to 60%. With a particular cell dosage (20 x 106), effectivity for cooperation with thymic function was the following in decreasing order: spleen, lymph nodes, thoracic duct cells, bone marrow, blood leukocytes, thymus, and Peyer's patch cells. Comparable results were obtained using spleen, thymus, and hemopoietic liver from newborn donors in association with thymic function. For similar cell dosages, newborn thymus cells were more effective than adult thymus in their cooperative effect with thymic function. Dispersed thymus cells in association with young adult bone marrow or newborn hemopoietic liver cells showed no synergism for the cooperative effect with thymic function in the present model. Using hemiallogeneic cells (F1 hybrid into parent) it was possible to show that restoration was mediated by proliferative expansion of the injected cells. This was indicated by specific tolerance to tissues of the other parental strain and by cellular chimerism, especially of lymphoid tissues, as indicated by chromosome markers and absence of significant numbers of immunocompetent cells of host origin. A population of paritally differentiated cells of hemopoietic origin, termed postthymic, sensitive to humoral activity of the thymus and present in the lymphohemopoietic tissues of adult and newborn mice is postulated to explain our results. These cells are postthymic and thymus dependent in the sense that they already received thymic influence, probably through traffic, and are incapable of self-renewal in absence of the thymus. Sensitivity to humoral activity of the thymus is characterized by proliferative expansion and/or a differentiative process eventually leading to larger numbers of competent cells.

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Selected References

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

  1. Axelrad M. A. Suppression of delayed hypersensitivity by antigen and antibody. Is a common precursor cell responsible for both delayed hypersensitivity and antibody formation? Immunology. 1968 Aug;15(2):159–171. [PMC free article] [PubMed] [Google Scholar]
  2. Claman H. N., Chaperon E. A. Immunologic complementation between thymus and marrow cells--a model for the two-cell theory of immunocompetence. Transplant Rev. 1969;1:92–113. doi: 10.1111/j.1600-065x.1969.tb00137.x. [DOI] [PubMed] [Google Scholar]
  3. Cooper G. N., Thonard J. C., Crosby R. L., Dalbow M. H. Immunological responses in rats following antigenic stimulation of Peyer's patches. II. Histological changes in germ-free animals. Aust J Exp Biol Med Sci. 1968 Aug;46(4):407–414. doi: 10.1038/icb.1968.34. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Davies A. J., Leuchars E., Wallis V., Koller P. C. The mitotic response of thymus-derived cells to antigenic stimulus. Transplantation. 1966 Jul;4(4):438–451. doi: 10.1097/00007890-196607000-00008. [DOI] [PubMed] [Google Scholar]
  6. Davis W. E., Jr, Cole L. J., Schaffer W. T. Studies on synergistic thymus-bone marrow cell interactions in immunological responses. Proc Soc Exp Biol Med. 1970 Jan;133(1):144–150. doi: 10.3181/00379727-133-34427. [DOI] [PubMed] [Google Scholar]
  7. FORD C. E., MICKLEM H. S. The thymus and lymph-nodes in radiation chimaeras. Lancet. 1963 Feb 16;1(7277):359–362. doi: 10.1016/s0140-6736(63)91385-0. [DOI] [PubMed] [Google Scholar]
  8. GOODMAN J. W. TRANSPLANTATION OF PERITONEAL FLUID CELLS. Transplantation. 1963 Jul;1:334–346. doi: 10.1097/00007890-196301030-00010. [DOI] [PubMed] [Google Scholar]
  9. Goldstein A. L., Slater F. D., White A. Preparation, assay, and partial purification of a thymic lymphocytopoietic factor (thymosin). Proc Natl Acad Sci U S A. 1966 Sep;56(3):1010–1017. doi: 10.1073/pnas.56.3.1010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. HARRIS J. E., FORD C. E. CELLULAR TRAFFIC OF THE THYMUS: EXPERIMENTS WITH CHROMOSOME MARKERS. EVIDENCE THAT THE THYMUS PLAYS AN INSTRUCTIONAL PART. Nature. 1964 Feb 29;201:884–885. doi: 10.1038/201884a0. [DOI] [PubMed] [Google Scholar]
  11. Mandel M. A. Isolation of mouse lymphocytes for immunologic studies by thoracic duct cannulation. Proc Soc Exp Biol Med. 1967 Nov;126(2):521–524. doi: 10.3181/00379727-126-32494. [DOI] [PubMed] [Google Scholar]
  12. Miller J. F., Mitchell G. F. Thymus and antigen-reactive cells. Transplant Rev. 1969;1:3–42. doi: 10.1111/j.1600-065x.1969.tb00135.x. [DOI] [PubMed] [Google Scholar]
  13. Miller J. F., Osoba D. Current concepts of the immunological function of the thymus. Physiol Rev. 1967 Jul;47(3):437–520. doi: 10.1152/physrev.1967.47.3.437. [DOI] [PubMed] [Google Scholar]
  14. Osoba D. The effects of thymus and other lymphoid organs enclosed in millipore diffusion chambers on neonatally thymectomized mice. J Exp Med. 1965 Sep 1;122(3):633–650. doi: 10.1084/jem.122.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Playfair J. H. Strain differences in the immune response of mice. II. Responses by neonatal cells in irradiated adult hosts. Immunology. 1968 Dec;15(6):815–826. [PMC free article] [PubMed] [Google Scholar]
  16. Sosin H., Hilgard H., Martinez C. The immunologic competence of mouse thymus cells measured by the graft vs. host spleen assay. J Immunol. 1966 Feb;96(2):189–195. [PubMed] [Google Scholar]
  17. Stutman O., Yunis E. J., Good R. A. Carcinogen-induced tumors of the thymus. 3. Restoration of neonatally thymectomized mice with thymomas in cell-impermeable chambers. J Natl Cancer Inst. 1969 Aug;43(2):499–508. [PubMed] [Google Scholar]
  18. Stutman O., Yunis E. J., Good R. A. Carcinogen-induced tumors of the thymus. I. Restoration of neonatally thymectomized mice with a functional thymoma. J Natl Cancer Inst. 1968 Dec;41(6):1431–1452. [PubMed] [Google Scholar]
  19. Stutman O., Yunis E. J., Good R. A. Carcinogen-induced tumors of the thymus. IV. Humoral influences of normal thymus and functional thymomas and influence of posthymectomy period on restoration. J Exp Med. 1969 Oct 1;130(4):809–819. doi: 10.1084/jem.130.4.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stutman O., Yunis E. J., Good R. A. Functional activity of a chemically induced thymic sarcoma. Lancet. 1967 May 27;1(7500):1120–1123. doi: 10.1016/s0140-6736(67)91704-7. [DOI] [PubMed] [Google Scholar]
  21. Stutman O., Yunis E. J., Good R. A. Reversal of post-thymectomy wasting in mice with immunocompetent cells: influence of histocompatibility differences. J Immunol. 1969 Jan;102(1):87–92. [PubMed] [Google Scholar]
  22. Stutman O., Yunis E. J., Good R. A. Studies on thymus function. II. Cooperative effect of newborn and embryonic hemopoietic liver cells with thymus function. J Exp Med. 1970 Sep 1;132(3):601–612. doi: 10.1084/jem.132.3.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Stutman O., Yunis E. J., Good R. A. Thymus: an essential factor in lymphoid repopulation. Transplant Proc. 1969 Mar;1(1):614–615. [PubMed] [Google Scholar]
  24. Stutman O., Yunis E. J., Good R. A. Tolerance induction with thymus grafts in neonatally thymectomized mice. J Immunol. 1969 Jul;103(1):92–99. [PubMed] [Google Scholar]
  25. Stutman O., Yunis E. J., Martinez C., Good R. A. Reversal of post-thymectomy wasting disease in mice by multiple thymus grafts. J Immunol. 1967 Jan;98(1):79–87. [PubMed] [Google Scholar]
  26. Stutman O., Yunis E. J., Teague P. O., Good R. A. Graft-versus-host reactions induced by transplantation of parental strain thymus in neonatally thymectomized F1 hybrid mice. Transplantation. 1968 Jul;6(4):514–523. doi: 10.1097/00007890-196807000-00002. [DOI] [PubMed] [Google Scholar]
  27. Stuttman O., Good R. A. Absence of synergism between thymus and bone marrow in graft-versus-host reactions. Proc Soc Exp Biol Med. 1969 Mar;130(3):848–852. doi: 10.3181/00379727-130-33670. [DOI] [PubMed] [Google Scholar]
  28. Tyan M. L., Cole L. J. Bone marrow as the major source of potential immunologically competent cells in the adult mouse. Nature. 1965 Dec 18;208(5016):1223–1224. doi: 10.1038/2081223a0. [DOI] [PubMed] [Google Scholar]
  29. Tyan M. L. Fetal liver and adult thymus cells: absence of synergism in graft-versus-host reactions. Proc Soc Exp Biol Med. 1969 Dec;132(3):1183–1185. doi: 10.3181/00379727-132-34392. [DOI] [PubMed] [Google Scholar]

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