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. 1982 Jul 1;156(1):79–89. doi: 10.1084/jem.156.1.79

Lymphocytic choriomeningitis virus killer T cells are lethal only in weakly disseminated murine infections

PMCID: PMC2186718  PMID: 6979608

Abstract

Two types of lymphocytic choriomeningitis (LCM) viruses were studied which, upon intracerebral injection into adult C3H mice, provoked either (a) acute fatal central nervous system (CNS) disease or (b) life- long persistent infection. Both virus types, (a) aggressive and (b) docile, had been found to induce LCM-specific lymphocytes with comparable in vitro lytic activity (11). Because the requirement for T cells in the development of adult LCM disease has been extensively documented, we sought other reasons for the lack of acute disease in mice infected with docile virus. A striking correlation was found between the outcome of the infection and spread of virus to visceral organs. Adoptive transfer experiments showed that a 300-plaque forming unit inoculum of docile virus induced a population of T cells in donor mice fully capable of causing CNS disease in identically infected recipients. This disease causing ability was lost if the interaction was delayed beyond 3 d after infection of the recipients, but could be preserved by lowering the size of the viral inoculum in the recipients. Furthermore, without adoptive transfer, very low intracerebral doses of docile virus (which mimicked the normally slow spread of aggressive virus) were lethal. On the other hand, very high doses of aggressive virus, which mimicked the normally rapid spread of docile virus, did not induce fatal CNS disease. The results suggest that rapid dissemination of the LCM infection creates multiple target organs which divert the focused lethal T cell attack on the brain.

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Selected References

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  1. Buchmeier M. J., Welsh R. M., Dutko F. J., Oldstone M. B. The virology and immunobiology of lymphocytic choriomeningitis virus infection. Adv Immunol. 1980;30:275–331. doi: 10.1016/s0065-2776(08)60197-2. [DOI] [PubMed] [Google Scholar]
  2. Cole G. A., Johnson E. D. Immune responses to LCM virus infection in vivo and in vitro. Mechanisms of immune-mediated disease. Bull World Health Organ. 1975;52(4-6):465–470. [PMC free article] [PubMed] [Google Scholar]
  3. Cole G. A., Nathanson N., Prendergast R. A. Requirement for theta-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease. Nature. 1972 Aug 11;238(5363):335–337. doi: 10.1038/238335a0. [DOI] [PubMed] [Google Scholar]
  4. Doherty P. C., Zinernagel R. M. Capacity of sensitized thymus-derived lymphocytes to induce fatal lymphocytic choriomeningitis is restricted by the H-2 gene complex. J Immunol. 1975 Jan;114(1 Pt 1):30–33. [PubMed] [Google Scholar]
  5. Doherty P. C., Zinkernagel R. M. H-2 compatibility is required for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. J Exp Med. 1975 Feb 1;141(2):502–507. doi: 10.1084/jem.141.2.502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. HOTCHIN J., BENSON L. THE PATHOGENESIS OF LYMPHOCYTIC CHORIOMENINGITIS IN MICE: THE EFFECTS OF DIFFERENT INOCULATION ROUTES AND THE FOOTPAD RESPONSE. J Immunol. 1963 Oct;91:460–468. [PubMed] [Google Scholar]
  8. Jacobson S., Dutko F. J., Pfau C. J. Determinants of spontaneous recovery and persistance in MDCK cells infected with lymphocytic choriomeningitis virus. J Gen Virol. 1979 Jul;44(1):113–122. doi: 10.1099/0022-1317-44-1-113. [DOI] [PubMed] [Google Scholar]
  9. Jacobson S., Friedman R. M., Pfau C. J. Interferon induction by lymphocytic choriomeningitis viruses correlates with maximum virulence. J Gen Virol. 1981 Dec;57(Pt 2):275–283. doi: 10.1099/0022-1317-57-2-275. [DOI] [PubMed] [Google Scholar]
  10. Jacobson S., Pfau C. J. Viral pathogenesis and resistance to defective interfering particles. Nature. 1980 Jan 17;283(5744):311–313. doi: 10.1038/283311a0. [DOI] [PubMed] [Google Scholar]
  11. Johnson E. D., Monjan A. A., Morse H. C., 3rd Lack of B-cell participation in acute lymphocyte choriomeningitis disease of the central nervous system. Cell Immunol. 1978 Mar 1;36(1):143–150. doi: 10.1016/0008-8749(78)90257-5. [DOI] [PubMed] [Google Scholar]
  12. Lehmann-Grube F. Dose-response relationships of lymphocytic choriomeningitis viruses in mice and L cell tube cultures. J Hyg (Lond) 1969 Jun;67(2):269–278. doi: 10.1017/s002217240004167x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. MIMS C. A. Intracerebral injections and the growth of viruses in the mouse brain. Br J Exp Pathol. 1960 Feb;41:52–59. [PMC free article] [PubMed] [Google Scholar]
  14. Pfau C. J., Valenti J. K., Jacobson S., Pevear D. C. Cytotoxic T cells are induced in mice infected with lymphocytic choriomeningitis virus strains of markedly different pathogenicities. Infect Immun. 1982 May;36(2):598–602. doi: 10.1128/iai.36.2.598-602.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Public Health Weekly Reports for JANUARY 10, 1936. Public Health Rep. 1936 Jan 10;51(2):29–52. [PMC free article] [PubMed] [Google Scholar]
  16. ROWE W. P., BLACK P. H., LEVEY R. H. PROTECTIVE EFFECT OF NEONATAL THYMECTOMY ON MOUSE LCM INFECTION. Proc Soc Exp Biol Med. 1963 Oct;114:248–251. doi: 10.3181/00379727-114-28643. [DOI] [PubMed] [Google Scholar]
  17. Rivière Y., Gresser I., Guillon J. C., Bandu M. T., Ronco P., Morel-Maroger L., Verroust P. Severity of lymphocytic choriomeningitis virus disease in different strains of suckling mice correlates with increasing amounts of endogenous interferon. J Exp Med. 1980 Sep 1;152(3):633–640. doi: 10.1084/jem.152.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Suzuki S., Hotchin J. Initiation of persistent lymphocytic choriomeningitis infection in adult mice. J Infect Dis. 1971 Jun;123(6):603–610. doi: 10.1093/infdis/123.6.603. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

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