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. 1977 May 1;145(5):1131–1143. doi: 10.1084/jem.145.5.1131

Mechanisms of suppression of cytotoxic T-cell responses in murine lymphocytic choriomeningitis virus infection

PMCID: PMC2180657  PMID: 300779

Abstract

The cytotoxic T-cell response to lymphocytic choriomeningitis (LCM) virus infection was suppressed either in vitro or in vivo by addition of a high level of syngeneic virus-infected cells or syngeneic cells from congenital LCM virus carriers to the environment of the responding cells. This effect was not duplicated by formaldehyde-fixed carrier cells, nor could it be accounted for by 'cold' target competition by carrier cells at the level of the cytotoxicity assay. Conversely, suppression was produced in vivo by water-lysed, ultrasonically treated carrier cell suspensions, or by a large dose of LCM virus equivalent to that contained in the carrier cells. Thus a high level of infectious virus was a common factor in all observed examples of suppression. Based upon this, the following hypothesis, a form of 'forbidden clone deletion,' was proposed to account for virus-specific cytotoxic T-cell tolerance in LCM virus congenital carriers, or in high dose suppression. A high level of virus in lymphoid tissues, while not cytopathic per se, may result in infection of all or most T cells; this then may lead to deletion either via 'suicide' of individual, infected, cytotoxic T cells with receptors specific for virus-induced antigenic patterns on their own surface membranes, or by mutual lysis of two adjacent T 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. Cihak J., Lehmann-Grube F. Persistent infection of mice with the virus of lymphocytic choriomeningitis: virus-specific immunological tolerance. Infect Immun. 1974 Nov;10(5):1072–1076. doi: 10.1128/iai.10.5.1072-1076.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cunningham A. J. Self-tolerance maintained by active suppressor mechanisms. Transplant Rev. 1976;31:23–43. doi: 10.1111/j.1600-065x.1976.tb01451.x. [DOI] [PubMed] [Google Scholar]
  3. Davidson W. F., Pang T., Blanden R. V., Doherty P. C. "Physiological interaction" does not explain the H-2 requirement for recognition of virus-infected cells by cytotoxic T cells. Aust J Exp Biol Med Sci. 1976 Oct;54(5):413–422. doi: 10.1038/icb.1976.41. [DOI] [PubMed] [Google Scholar]
  4. Doherty P. C., Zinkernagel R. M., Ramshaw I. A. Specificity and development of cytotoxic thymus-derived lymphocytes in lymphocytic choriomeningitis. J Immunol. 1974 Apr;112(4):1548–1552. [PubMed] [Google Scholar]
  5. Doherty P. C., Zinkernagel R. M. T-cell-mediated immunopathology in viral infections. Transplant Rev. 1974;19(0):89–120. doi: 10.1111/j.1600-065x.1974.tb00129.x. [DOI] [PubMed] [Google Scholar]
  6. Dunlop M. B., Blanden R. V. Secondary cytotoxic cell response to lymphocytic choriomeningitis virus. I. Kinetics of induction in vitro and yields of effector cells. Immunology. 1976 Aug;31(2):171–180. [PMC free article] [PubMed] [Google Scholar]
  7. Dunlop M. B., Doherty P. C., Zinkernagel R. M., Blanden R. V. Secondary cytotoxic cell response to lymphocytic choriomeningitis virus II. Nature and specificity of effector cells. Immunology. 1976 Aug;31(2):181–186. [PMC free article] [PubMed] [Google Scholar]
  8. Gardner I., Bowern N. A., Blanden R. V. Cell-mediated cytotoxicity against ectromelia virus-infected target cells. I. Specificity and kinetics. Eur J Immunol. 1974 Feb;4(2):63–67. doi: 10.1002/eji.1830040202. [DOI] [PubMed] [Google Scholar]
  9. Gershon R. K. A disquisition on suppressor T cells. Transplant Rev. 1975;26:170–185. doi: 10.1111/j.1600-065x.1975.tb00179.x. [DOI] [PubMed] [Google Scholar]
  10. Gilden D. H., Cole G. A., Monjan A. A., Nathanson N. Immunopathogenesis of acute central nervous system disease produced by lymphocytic choriomeningitis virus. I. Cyclophosphamide-mediated induction by the virus-carrier state in adult mice. J Exp Med. 1972 Apr 1;135(4):860–873. doi: 10.1084/jem.135.4.860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gilden D. H., Cole G. A., Nathanson N. Immunopathogenesis of acute central nervous system disease produced by lymphocytic choriomeningitis virus. II. Adoptive immunization of virus carriers. J Exp Med. 1972 Apr 1;135(4):874–889. doi: 10.1084/jem.135.4.874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Greaves M., Janossy G. Elicitation of selective T and B lymphocyte responses by cell surface binding ligands. Transplant Rev. 1972;11:87–130. doi: 10.1111/j.1600-065x.1972.tb00047.x. [DOI] [PubMed] [Google Scholar]
  13. Kuppers R. C., Henney C. S. Evidence for direct linkage between antigen recognition and lytic expression in effector T cells. J Exp Med. 1976 Mar 1;143(3):684–689. doi: 10.1084/jem.143.3.684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Marker O., Volkert M. Studies on cell-mediated immunity to lymphocytic choriomeningitis virus in mice. J Exp Med. 1973 Jun 1;137(6):1511–1525. doi: 10.1084/jem.137.6.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mims C. A., Blanden R. V. Antiviral action of immune lymphocytes in mice infected with lymphocytic choriomeningitis virus. Infect Immun. 1972 Nov;6(5):695–698. doi: 10.1128/iai.6.5.695-698.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Pang T., Blanden R. V. The role of adherent cells in the secondary cell-mediated response in vitro to a natural poxvirus pathogen. Aust J Exp Biol Med Sci. 1976 Dec;54(6):559–571. doi: 10.1038/icb.1976.57. [DOI] [PubMed] [Google Scholar]
  18. Traub E. A FILTERABLE VIRUS RECOVERED FROM WHITE MICE. Science. 1935 Mar 22;81(2099):298–299. doi: 10.1126/science.81.2099.298. [DOI] [PubMed] [Google Scholar]
  19. Volkert M., Larsen J. H. Immunological tolerance to viruses. Prog Med Virol. 1965;7:160–207. [PubMed] [Google Scholar]
  20. Zinkernagel R. M., Doherty P. C. Characteristics of the interaction in vitro between cytotoxic thymus-derived lymphocytes and target monolayers infected with lymphocytic choriomeningitis virus. Scand J Immunol. 1974;3(3):287–294. doi: 10.1111/j.1365-3083.1974.tb01259.x. [DOI] [PubMed] [Google Scholar]
  21. Zinkernagel R. M., Doherty P. C. Cytotoxic thymus-derived lymphocytes in cerebrospinal fluid of mice with lymphocytic choriomeningitis. J Exp Med. 1973 Nov 1;138(5):1266–1269. doi: 10.1084/jem.138.5.1266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zinkernagel R. M., Welsh R. M. H-2 compatibility requirement for virus-specific T cell-mediated effector functions in vivo. I. Specificity of T cells conferring antiviral protection against lymphocytic choriomeningitis virus is associated with H-2K and H-2D. J Immunol. 1976 Nov;117(5 Pt 1):1495–1502. [PubMed] [Google Scholar]

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