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. 1969 Jan;16(1):15–23.

On the induction of immunological tolerance to a self-reproducing antigen

J Hannover Larsen
PMCID: PMC1409561  PMID: 4977003

Abstract

Inoculation of a dose of 1000 LD50 of LCM virus intraperitoneally into newborn mice within the first 18 hours of life always resulted in the development of a complete and permanent state of tolerance to the virus as judged by a life-long viraemia with titres of [unk] 102.3 and complement fixation (CF) titres of <4.

Sixteen litters of outbred white Swiss mice were inoculated intraperitoneally with this virus dosage at an age of 2–9 days. A total of 103 babies were inoculated. Of these babies sixty survived the first 2 weeks of life. They were followed for 24 weeks with regard to the course of the viraemia and CF-antibody production.

On the basis of the values obtained in this manner in the individual mouse seven types of course could be distinguished. These represented the following immunological phenomena: (1) complete and permanent tolerance; (2) disappearance of the viraemia and antibody formation; (3) disappearance of the viraemia without antibody formation; (4) permanent viraemia with antibody formation; and (5) temporary, incomplete tolerance as illustrated both by temporary antibody formation with constant viraemia and by temporary viraemia elimination without antibody formation.

The results indicate that a dissociation of the immunological response of the mouse to LCM virus can take place, presumably representing a state of split tolerance. Furthermore the results indicate that specifically reactive cells can be present in an apparently completely tolerant animal. These findings are discussed in the light of the hypothesis that complete tolerance represents the maximum degree of specific immunosuppression.

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Selected References

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

  1. BILLINGHAM R. E., BRENT L., MEDAWAR P. B. The antigenic stimulus in transplantation immunity. Nature. 1956 Sep 8;178(4532):514–519. doi: 10.1038/178514a0. [DOI] [PubMed] [Google Scholar]
  2. BRENT L., GOWLAND G. Cellular dose and age of host in the induction of tolerance. Nature. 1961 Dec 30;192:1265–1267. doi: 10.1038/1921265a0. [DOI] [PubMed] [Google Scholar]
  3. CLARKE D. H., CASALS J. Techniques for hemagglutination and hemagglutination-inhibition with arthropod-borne viruses. Am J Trop Med Hyg. 1958 Sep;7(5):561–573. doi: 10.4269/ajtmh.1958.7.561. [DOI] [PubMed] [Google Scholar]
  4. Celada F. Quantitative studies of the adoptive immunological memory in mice. I. An age-dependent barrier to syngeneic transplantation. J Exp Med. 1966 Jul 1;124(1):1–14. doi: 10.1084/jem.124.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hirsch M. S., Murphy F. A., Hicklin M. D. Immunopathology of lymphocytic choriomeningitis viurs infection of newborn mice. Antithymocyte serum effects on glomerulonephritis and wasting disease. J Exp Med. 1968 Apr 1;127(4):757–766. doi: 10.1084/jem.127.4.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Larsen J. H. Studies on immunological tolerance to LCM virus. 9. Induction of immunological tolerance to the virus in the adult mouse. Acta Pathol Microbiol Scand. 1968;73(1):106–114. doi: 10.1111/j.1699-0463.1968.tb00484.x. [DOI] [PubMed] [Google Scholar]
  7. MICHIE D., HOWARD J. G. Transplantation tolerance and immunological immaturity. Ann N Y Acad Sci. 1962 Oct 24;99:670–679. doi: 10.1111/j.1749-6632.1962.tb45350.x. [DOI] [PubMed] [Google Scholar]
  8. Oldstone M. B., Dixon F. J. Lymphocytic choriomeningitis: production of antibody by "tolerant" infected mice. Science. 1967 Dec 1;158(3805):1193–1195. doi: 10.1126/science.158.3805.1193. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. VOLKERT M., LARSEN J. H., PFAU C. STUDIES ON IMMUNOLOGICAL TOLERANCE TO LCM VIRUS. 4. THE QUESTION OF IMMUNITY IN ADOPTIVELY IMMUNIZED VIRUS CARRIERS. Acta Pathol Microbiol Scand. 1964;61:268–282. doi: 10.1111/apm.1964.61.2.268. [DOI] [PubMed] [Google Scholar]
  12. VOLKERT M., LARSEN J. H. STUDIES ON IMMUNOLOGICAL TOLERANCE TO LCM VIRUS. 3. DURATION AND MAXIMAL EFFECT OF ADOPTIVE IMMUNIZATION OF VIRUS CARRIERS. Acta Pathol Microbiol Scand. 1964;60:577–587. doi: 10.1111/apm.1964.60.4.577. [DOI] [PubMed] [Google Scholar]
  13. VOLKERT M., LARSEN J. H. STUDIES ON IMMUNOLOGICAL TOLERANCE TO LCM VIRUS. 5. THE INDUCTION OF TOLERANCE TO THE VIRUS. Acta Pathol Microbiol Scand. 1965;63:161–171. doi: 10.1111/apm.1965.63.2.161. [DOI] [PubMed] [Google Scholar]
  14. VOLKERT M., LARSEN J. H. STUDIES ON IMMUNOLOGICAL TOLERANCE TO LCM VIRUS. 6. IMMUNITY CONFERRED ON TOLERANT MICE BY IMMUNE SERUM AND BY GRAFTS OF HOMOLOGOUS LYMPHOID CELLS. Acta Pathol Microbiol Scand. 1965;63:172–180. doi: 10.1111/apm.1965.63.2.172. [DOI] [PubMed] [Google Scholar]
  15. VOLKERT M. STUDIES ON IMMUNOLOGICAL TOLERANCE TO LCM VIRUS. 2. TREATMENT OF VIRUS CARRIER MICE BY ADOPTIVE IMMUNIZATION. Acta Pathol Microbiol Scand. 1963;57:465–487. [PubMed] [Google Scholar]
  16. Volkert M., Larsen J. H. Immunological tolerance to viruses. Prog Med Virol. 1965;7:160–207. [PubMed] [Google Scholar]

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