Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1972 Mar 31;135(4):874–889. doi: 10.1084/jem.135.4.874

IMMUNOPATHOGENESIS OF ACUTE CENTRAL NERVOUS SYSTEM DISEASE PRODUCED BY LYMPHOCYTIC CHORIOMENINGITIS VIRUS

II. ADOPTIVE IMMUNIZATION OF VIRUS CARRIERS

Donald H Gilden 1, Gerald A Cole 1, Neal Nathanson 1
PMCID: PMC2139163  PMID: 4622913

Abstract

Lymphocytic choriomeningitis (LCM) virus carriers were established by intracerebral inoculation of adult BALB/c mice followed by a single dose of cyclophosphamide (CY) (150 mg/kg) 3 days after infection, and by intracerebral injection within 24 hr of birth. These carriers were then adoptively immunized with spleen cells or serum from immune or normal BALB/c donors. Transfer of immune spleen cells into drug-induced carriers consistently resulted in acutely fatal choriomeningitis, histologically strikingly similar to classical LCM. Normal spleen cells or immune serum failed to produce either central nervous system (CNS) pathology or illness with any regularity. In addition, focal necrosis of the cerebellum was seen after adoptive immunization of drug-induced carriers but only when mice received cells at least 3 wk after inoculation, which is probably explained by the gradual spread of infection from membranes to the neural parenchyma during the first month after establishment of the carrier state in adult mice. Immune spleen cells, when transferred to neonatal carriers, led to a decrease in virus titers in blood and brains and to development of antibody without acute CNS disease. It appears that the production of fatal choriomeningitis after LCM infection is determined in part by the distribution of viral antigen, and this is markedly different in neonatal and drug-induced carriers at the time of cell transfer. Another factor of potential importance is the much higher level of circulating viral antigen in the plasma of neonatal than in that of drug-induced LCM carriers. Classical LCM disease can only be transferred by immune lymphoid cells and not by antiserum. Furthermore, little or no complement-fixing (CF) antibody was found in the plasma of mice dying of acute choroiditis. These observations strongly suggest that acute choroiditis is dependent upon the cell-mediated immune response.

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

Selected References

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

  1. Borden E. C., Murphy F. A., Nathanson N., Monath T. P. Effect of antilymphocyte serium on tacaribe virus infection in infant mice. Infect Immun. 1971 Mar;3(3):466–471. doi: 10.1128/iai.3.3.466-471.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cole G. A., Gilden D. H., Monjan A. A., Nathanson N. Lymphocytic choriomeningitis virus: pathogenesis of acute central nervous system disease. Fed Proc. 1971 Nov-Dec;30(6):1831–1841. [PubMed] [Google Scholar]
  3. 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]
  4. HOTCHIN J. The biology of lymphocytic choriomeningitis infection: virus-induced immune disease. Cold Spring Harb Symp Quant Biol. 1962;27:479–499. doi: 10.1101/sqb.1962.027.001.046. [DOI] [PubMed] [Google Scholar]
  5. HOTCHIN J., WEIGAND H. The effects of pretreatment with x-rays on the pathogenesis of lymphocytic choriomeningitis in mice. I. Host survival, virus multiplication and leukocytosis. J Immunol. 1961 Dec;87:675–681. [PubMed] [Google Scholar]
  6. 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]
  7. Larsen J. H. The effect of immunosuppressive therapy of the murine lymphocytic choriomeningitis virus infection. Acta Pathol Microbiol Scand. 1969;77(3):433–446. doi: 10.1111/j.1699-0463.1969.tb04250.x. [DOI] [PubMed] [Google Scholar]
  8. Levine S., Hoenig E. M., Kies M. W. Allergic encephalomyelitis: immunologically specific inhibition of cellular passive transfer by encephalitogenic basic proteins. Clin Exp Immunol. 1970 Apr;6(4):503–517. [PMC free article] [PubMed] [Google Scholar]
  9. Oldstone M. B., Dixon F. J. Pathogenesis of chronic disease associated with persistent lymphocytic choriomeningitis viral infection. I. Relationship of antibody production to disease in neonatally infected mice. J Exp Med. 1969 Mar 1;129(3):483–505. doi: 10.1084/jem.129.3.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Oldstone M. B., Dixon F. J. Pathogenesis of chronic disease associated with persistent lymphocytic choriomeningitis viral infection. II. Relationship of the anti-lymphocytic choriomeningitis immune response to tissue injury in chronic lymphocytic choriomeningitis disease. J Exp Med. 1970 Jan 1;131(1):1–19. doi: 10.1084/jem.131.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Silverstein A. M., Borek F. Desensitization studies of delayed hypersensitivity, with special reference to the possible role of high-affinity antibodies. J Immunol. 1966 Jun;96(6):953–959. [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  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., Larsen J. H. Immunological tolerance to viruses. Prog Med Virol. 1965;7:160–207. [PubMed] [Google Scholar]
  16. WILSNACK R. E., ROWE W. P. IMMUNOFLUORESCENT STUDIES OF THE HISTOPATHOGENESIS OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS INFECTION. J Exp Med. 1964 Nov 1;120:829–840. doi: 10.1084/jem.120.5.829. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES