Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1973 Jan 31;137(2):291–300. doi: 10.1084/jem.137.2.291

ACTIVE SUPPRESSION AS A POSSIBLE MECHANISM OF TOLERANCE IN TETRAPARENTAL MICE

S Michael Phillips 1, Thomas G Wegmann 1
PMCID: PMC2139486  PMID: 4539846

Abstract

Previous work has indicated that tetraparental mice, chimeric since the eight-cell stage because of embryo fusion using histoincompatible strain combinations, possess autospecific immune cells and blocking antibodies. Although this phenomenon has been demonstrated in vitro, it may have relevance to the self-tolerance shown by these mice in vivo. The experiments described here indicate that spleen cells from tetraparental mice can block mixed lymphocyte reactions between the two parental cell types, but not between unrelated strains. Furthermore, this suppressive ability is not affected by an otherwise effective treatment of the tetraparental spleen cells with anti-θ antibody and complement. The in vitro experimental system elaborated here should help to characterize the cell type responsible for the suppression.

Full Text

The Full Text of this article is available as a PDF (645.8 KB).

Selected References

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

  1. Adler W. H., Takiguchi T., Marsh B., Smith R. T. Cellular recognition by mouse lymphocytes in vitro. I. Definition of a new technique and results of stimulation by phytohemagglutinin and specific antigens. J Exp Med. 1970 Jun 1;131(6):1049–1078. doi: 10.1084/jem.131.6.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allison A. C. Unresponsiveness to self antigens. Lancet. 1971 Dec 25;2(7739):1401–1403. doi: 10.1016/s0140-6736(71)90673-8. [DOI] [PubMed] [Google Scholar]
  3. Atkins R. C., Ford W. L. The effect of lymphocytes and serum from tolerant rats on the graft-versus-host activity of normal lymphocytes. Transplantation. 1972 Apr;13(4):442–444. doi: 10.1097/00007890-197204000-00019. [DOI] [PubMed] [Google Scholar]
  4. Bach F. H., Voynow N. K. One-way stimulation in mixed leukocyte cultures. Science. 1966 Jul 29;153(3735):545–547. doi: 10.1126/science.153.3735.545. [DOI] [PubMed] [Google Scholar]
  5. Burnet F. M. A reassessment of the forbidden clone hypothesis of autoimmune disease. Aust J Exp Biol Med Sci. 1972 Feb;50(1):1–9. doi: 10.1038/icb.1972.1. [DOI] [PubMed] [Google Scholar]
  6. Cohen I. R., Globerson A., Feldman M. Autosensitization in vitro. J Exp Med. 1971 Apr 1;133(4):834–845. doi: 10.1084/jem.133.4.834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cohen I. R., Wekerle H. Autosensitization of lymphocytes against thymus reticulum cells. Science. 1972 Jun 23;176(4041):1324–1325. doi: 10.1126/science.176.4041.1324. [DOI] [PubMed] [Google Scholar]
  8. Elkins W. L. Cellular control of lymphocytes initiating graft vs. host reactions. Cell Immunol. 1972 Jun;4(2):192–196. doi: 10.1016/0008-8749(72)90020-2. [DOI] [PubMed] [Google Scholar]
  9. Hellström K. E., Hellström I. Immunological enhancement as studied by cell culture techniques. Annu Rev Microbiol. 1970;24:373–398. doi: 10.1146/annurev.mi.24.100170.002105. [DOI] [PubMed] [Google Scholar]
  10. Jacobson E. B., Herzenberg L. A., Riblet R., Herzenberg L. A. Active suppression of immunoglobulin allotype synthesis. II. Transfer of suppressing factor with spleen cells. J Exp Med. 1972 May 1;135(5):1163–1176. doi: 10.1084/jem.135.5.1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mintz B., Silvers W. K. "Intrinsic" immunological tolerance in allophenic mice. Science. 1967 Dec 15;158(3807):1484–1486. doi: 10.1126/science.158.3807.1484. [DOI] [PubMed] [Google Scholar]
  12. Phillips S. M., Carpenter C. B., Merrill J. P. Cellular immunity in the mouse. I. In vitro lymphocyte reactivity. Cell Immunol. 1972 Oct;5(2):235–248. doi: 10.1016/0008-8749(72)90050-0. [DOI] [PubMed] [Google Scholar]
  13. Phillips S. M., Carpenter C. B., Merrill J. P. Cellular immunity in the mouse. II. Correlation of in vivo and in vitro phenomena. Cell Immunol. 1972 Oct;5(2):249–263. doi: 10.1016/0008-8749(72)90051-2. [DOI] [PubMed] [Google Scholar]
  14. Phillips S. M., Martin W. J., Shaw A. R., Wegmann T. G. Serum-mediated immunological non-reactivity between histoincompatible cells in tetraparental mice. Nature. 1971 Nov 19;234(5325):146–148. doi: 10.1038/234146a0. [DOI] [PubMed] [Google Scholar]
  15. Pierce G. E. In vitro effects of syngeneic lymphocytes and serum on F 1 hybrid fibroblasts. Cell Immunol. 1972 Jan;3(1):150–155. doi: 10.1016/0008-8749(72)90236-5. [DOI] [PubMed] [Google Scholar]
  16. TARKOWSKI A. K. Mouse chimaeras developed from fused eggs. Nature. 1961 Jun 3;190:857–860. doi: 10.1038/190857a0. [DOI] [PubMed] [Google Scholar]
  17. Voisin G. A., Kinsky R. G., Maillard J. Réativité immunitaire et anticorps facilitants chez des animaux tolérants aux homogreffes. Ann Inst Pasteur (Paris) 1968 Nov;115(5):855–879. [PubMed] [Google Scholar]
  18. Wegmann T. G., Gilman J. G. Chimerism for three genetic systems in tetraparental mice. Dev Biol. 1970 Mar;21(3):281–291. doi: 10.1016/0012-1606(70)90125-9. [DOI] [PubMed] [Google Scholar]
  19. Wegmann T. G., Hellström I., Hellström K. E. Immunological tolerance: "forbidden clones" allowed in tetraparental mice. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1644–1647. doi: 10.1073/pnas.68.7.1644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wilson D. B., Nowell P. C. Quantitative studies on the mixed lymphocyte interaction in rats. IV. Immunologic potentiality of the responding cells. J Exp Med. 1970 Feb;131(2):391–407. doi: 10.1084/jem.131.2.391. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES