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. 1972 May 1;135(5):1185–1203. doi: 10.1084/jem.135.5.1185

IMMUNE STATUS OF MICE TOLERANT OF LIVING CELLS

II. CONTINUOUS PRESENCE AND NATURE OF FACILITATION-ENHANCING ANTIBODIES IN TOLERANT ANIMALS

G A Voisin 1, R G Kinsky 1, H T Duc 1
PMCID: PMC2138981  PMID: 4623319

Abstract

CBA mice were rendered highly tolerant to A/Jax cells by neonatal intravenous injections of (CBA x A)F1 spleen cells. The high degree of tolerance was ascertained by the absence of circulating antibodies detected in the sera by the usual tests and by the perfect state of A skin grafts during all the experiments. Tolerant sera (sera from tolerant animals) were studied at three periods of tolerance: before skin test grafting, from 2 to 11 wk after grafting, and at time of sacrifice at almost 6 months of age. The tolerant sera were shown to have specific facilitation-enhancing properties promoting the take and growth of A/Jax sarcoma (SaI and /Sa 15091a grafted on normal CBA mice. These properties were present throughout the duration of the experiments, showing that they were not the result of a beginning interruption of tolerance. The tolerant sera, although lacking the usual serological properties (hemagglutination, hemolysis, cytotoxicity, passive cutaneous anaphylaxis) had, however, specific synergistic hemagglutinating properties (increasing the hemagglutinating titer of a reference immune serum). Antibodies giving direct specific hemagglutination could be extracted from spleens of 20% of highly tolerant mice. The tolerant sera were also found to contain more IgG1 and more IgA than normal sera while they contained normal quantities of the complement-fixing immunoglobulins IgG2 and IgM. Fractionation of tolerant sera on DEAE chromatography column confirmed the data concerning immunoglobulin classes and demonstrated direct specific serological activities undetected in unfractionated sera: a weak hemolysis in the most cationic fractions and a weak hemagglutination in the middle fractions. Synergistic hemagglutination, detected in unfractionated serum, was localized in fast anionic fractions containing high IgA concentration, along with facilitation-enhancing activity, thus confirming a link suggested previously between these three properties. The relation between immunological tolerance and facilitating antibodies was discussed in the light of the fact that antibodies, possibly of a particular class continuously present at low dose in the sera of highly tolerant animals, are able to transfer (at least partly) this state of tolerance provided a sensitive test system is utilized.

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Selected References

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  1. Asherson G. L., Stone S. H. Selective and specific inhibition of 24 hour skin reactions in the guinea-pig. I. Immune deviation: description of the phenomenon and the effect of splenectomy. Immunology. 1965 Sep;9(3):205–217. [PMC free article] [PubMed] [Google Scholar]
  2. Asherson G. L., Zembala M., Barnes R. M. The mechanism of immunological unresponsiveness to picryl chloride and the possible role of antibody mediated depression. Clin Exp Immunol. 1971 Jul;9(1):111–121. [PMC free article] [PubMed] [Google Scholar]
  3. CHOUROULINKOV I., BOYSE E. A., OLD L. J. Cytotoxic activity of isoantibody on sarcoma I. Proc Soc Exp Biol Med. 1962 Nov;111:263–265. doi: 10.3181/00379727-111-27762. [DOI] [PubMed] [Google Scholar]
  4. Chard T., French M. E., Batchelor J. R. Enhancement of the C57BL leukemia E.L.4 by Fab fragments of isoantibody. Transplantation. 1967 Sep 5;5(5):1266–1272. doi: 10.1097/00007890-196709000-00004. [DOI] [PubMed] [Google Scholar]
  5. Chard T. Immunological enhancement by mouse isoantibodies: the importance of complement fixation. Immunology. 1968 Apr;14(4):583–589. [PMC free article] [PubMed] [Google Scholar]
  6. Crowle A. J., Hu C. C. Adoptive transfer of immunologic tolerance into normal mice. J Immunol. 1969 Dec;103(6):1242–1247. [PubMed] [Google Scholar]
  7. Crowle A. J., Hu C. C. Investigation of the mechanisms by whick "enhancing" antiserum prevents induction of delayed hypersensitivity to protein antigens in mice. J Allergy. 1969 Apr;43(4):209–223. doi: 10.1016/0021-8707(69)90064-1. [DOI] [PubMed] [Google Scholar]
  8. DEUTSCH H. F. II. Separation of antibody-active proteins from various animal sera by ethanol fractionation techniques. Methods Med Res. 1952;5:284–300. [PubMed] [Google Scholar]
  9. Diener E., Feldmann M. Antibody-mediated suppression of the immune response in vitro. II. A new approach to the phenomenon of immunological tolerance. J Exp Med. 1970 Jul 1;132(1):31–43. doi: 10.1084/jem.132.1.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. FAHEY J. L., BARTH W. F. THE IMMUNOGLOBULINS OF MICE. 4. SERUM IMMUNOGLOBULIN CHANGES FOLLOWING BIRTH. Proc Soc Exp Biol Med. 1965 Mar;118:596–600. doi: 10.3181/00379727-118-29914. [DOI] [PubMed] [Google Scholar]
  11. FAHEY J. L., SELL S. THE IMMUNOGLOBULINS OF MICE. V. THE METABOLIC (CATABOLIC) PROPERTIES OF FIVE IMMUNOGLOBULIN CLASSES. J Exp Med. 1965 Jul 1;122:41–58. doi: 10.1084/jem.122.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Feldmann M., Diener E. Antibody-mediated suppression of the immune response in vitro. 3. Low zone tolerance in vitro. Immunology. 1971 Sep;21(3):387–404. [PMC free article] [PubMed] [Google Scholar]
  13. GORER P. A., MIKULSKA Z. B., O'GORMAN P. The time of apperance of isoantibodies during the homograft response to mouse tumours. Immunology. 1959 Jul;2:211–218. [PMC free article] [PubMed] [Google Scholar]
  14. GORER P. A., MIKULSKA Z. B. The antibody response to tumor inoculation; improved methods of antibody detection. Cancer Res. 1954 Oct;14(9):651–655. [PubMed] [Google Scholar]
  15. HILDEMANN W. H. A method for detecting hemolysins in mouse isoimmune serums. Transplant Bull. 1957 Oct;4(4):148–149. [PubMed] [Google Scholar]
  16. Hellström K. E., Hellström I., Brawn J. Abrogation of cellular immunity to antigenically foreign mouse embryonic cells by a serum factor. Nature. 1969 Nov 29;224(5222):914–915. doi: 10.1038/224914a0. [DOI] [PubMed] [Google Scholar]
  17. Kinsky R., Voisin G. A., Hilgert I., Duc H. T. Biological properties of transplantation immune sera. II. PCA in mice with H-2 antigens. Transplantation. 1971 Sep;12(3):171–175. doi: 10.1097/00007890-197109000-00004. [DOI] [PubMed] [Google Scholar]
  18. Linscott W. D. Effect of cell surface antigen density on immunological enhancement. Nature. 1970 Nov 28;228(5274):824–827. doi: 10.1038/228824a0. [DOI] [PubMed] [Google Scholar]
  19. MARTINEZ C., SMITH J. M., SHAPIRO F., GOOD R. A. Transfer of acquired immunological tolerance of skin homografts in mice joined in parabiosis. Proc Soc Exp Biol Med. 1959 Nov;102:413–417. doi: 10.3181/00379727-102-25268. [DOI] [PubMed] [Google Scholar]
  20. Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
  21. ROWLEY D. A., FITCH F. W. THE MECHANISM OF TOLERANCE PRODUCED IN RATS TO SHEEP ERYTHROCYTES. I. PLAQUE-FORMING CELL AND ANTIBODY RESPONSE TO SINGLE AND MULTIPLE INJECTIONS OF ANTIGEN. J Exp Med. 1965 May 1;121:671–681. doi: 10.1084/jem.121.5.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. ROWLEY D. A., FITCH F. W. THE MECHANISM OF TOLERANCE PRODUCED IN RATS TO SHEEP ERYTHROCYTES. II. THE PLAQUE-FORMING CELL AND ANTIBODY RESPONSE TO MULTIPLE INJECTIONS OF ANTIGEN BEGUN AT BIRTH. J Exp Med. 1965 May 1;121:683–695. doi: 10.1084/jem.121.5.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schwarz M. R. The mixed lymphocyte reaction: an in vitro test for tolerance. J Exp Med. 1968 May 1;127(5):879–890. doi: 10.1084/jem.127.5.879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Takasugi M., Hildemann W. H. Regulation of immunity toward allogeneic tumors in mice. I. Effect of antiserum fractions on tumor growth. J Natl Cancer Inst. 1969 Oct;43(4):843–856. [PubMed] [Google Scholar]
  25. Voisin G. A. Immunity and tolerance: a unified concept. Cell Immunol. 1971 Dec;2(6):670–689. doi: 10.1016/0008-8749(71)90014-1. [DOI] [PubMed] [Google Scholar]
  26. Voisin G. A. Immunological facilitation, a broadening of the concept of the enhancement phenomenon. Prog Allergy. 1971;15:328–485. [PubMed] [Google Scholar]
  27. Voisin G. A., Kinsky R. G., Jansen F. K. Transplantation immunity: localization in mouse serum of antibodies responsible for haemagglutination, cytotoxicity and enhancement. Nature. 1966 Apr 9;210(5032):138–139. doi: 10.1038/210138a0. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Voisin G. A., Kinsky R., Jansen F., Bernard C. Biological properties of antibody classes in transplantation immune sera. Transplantation. 1969 Nov;8(5):618–632. doi: 10.1097/00007890-196911000-00008. [DOI] [PubMed] [Google Scholar]
  30. Voisin G. A., Kinsky R., Maillard J. Protection against homologous disease in hybrid mice by passive and active immunological enhancement-facilitation. Transplantation. 1968 Mar;6(2):187–202. doi: 10.1097/00007890-196803000-00005. [DOI] [PubMed] [Google Scholar]
  31. Voisin G. A., Kinsky R., Maillard J. Protection contre la maladie homologue par facilitation immunologique (enhancement phenomenon) induite passivement et activement. Ann Inst Pasteur (Paris) 1967 Oct;113(4):521–547. [PubMed] [Google Scholar]
  32. 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]

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