Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1990 Oct;137(4):907–912.

T-lymphocyte effects on murine cytomegalovirus pulmonary infection.

M Kadima-Nzuji 1, J E Craighead 1
PMCID: PMC1877540  PMID: 2171343

Abstract

Cytomegalovirus (CMV) infections were induced in male BALB/c mice treated with rat monoclonal antibodies (MAb) to deplete selectively CD8 and CD4 cell populations in vivo. The animals were then inoculated intraperitoneally with murine CMV and the infection was monitored virologically and histologically. High concentrations of virus were found in the lungs of mice depleted of CD4 or both CD4 and CD8 cells. These animals developed pulmonary infections that persisted for at least 49 days after inoculation. In contrast, immunologically intact mice and those administered anti-CD8 MAb experienced only a transient infection of the lungs. Focal interstitial infiltrates of mononuclear cells were demonstrated in pulmonary tissues of CD4 MAb-treated animals, but not in normal mice and those receiving the CD8 MAb. Adoptive transfer of CD4 cells to animals (rendered immune-incompetent by thymectomy and irradiation) protected against pulmonary infection and the development of interstitial pneumonia. Mice treated with CD4 MAb failed to produce specific CMV antibody, whereas the depletion of CD8 cells had no effect on antibody elaboration. Administration of anti-CD4 and CD8 MAb did not affect virus replication in the salivary glands, the preferential site for CMV infection in the mouse. Induction of pulmonary infection and interstitial pneumonia by CMV in BALB/c mice is mediated by CD4 T cells.

Full text

PDF
911

Images in this article

910Figure 3
on p.910

Selected References

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

  1. Bia F. J., Lucia H. L., Bia M. J., Vine W., Tuttle A. Effects of cyclosporine on the pathogenesis of primary cytomegalovirus infection in the guinea pig. Intervirology. 1985;24(3):154–165. doi: 10.1159/000149635. [DOI] [PubMed] [Google Scholar]
  2. Brody A. R., Craighead J. E. A simple perfusion apparatus for lung fixation. Proc Soc Exp Biol Med. 1973 Jun;143(2):388–390. doi: 10.3181/00379727-143-37327. [DOI] [PubMed] [Google Scholar]
  3. Brody A. R., Craighead J. E. Pathogenesis of pulmonary cytomegalovirus infection in immunosuppressed mice. J Infect Dis. 1974 Jun;129(6):677–689. doi: 10.1093/infdis/129.6.677. [DOI] [PubMed] [Google Scholar]
  4. Craighead J. E. Cytomegalovirus pulmonary disease. Pathobiol Annu. 1975;5:197–220. [PubMed] [Google Scholar]
  5. Craighead J. E., Hanshaw J. B., Carpenter C. B. Cytomegalovirus infection after renal allotransplantation. JAMA. 1967 Sep 4;201(10):725–728. [PubMed] [Google Scholar]
  6. Craighead J. E. Pulmonary cytomegalovirus infection in the adult. Am J Pathol. 1971 Jun;63(3):487–504. [PMC free article] [PubMed] [Google Scholar]
  7. Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
  8. Erlich K. S., Mills J., Shanley J. D. Effects of L3T4+ lymphocyte depletion on acute murine cytomegalovirus infection. J Gen Virol. 1989 Jul;70(Pt 7):1765–1771. doi: 10.1099/0022-1317-70-7-1765. [DOI] [PubMed] [Google Scholar]
  9. Grundy J. E., Shanley J. D., Griffiths P. D. Is cytomegalovirus interstitial pneumonitis in transplant recipients an immunopathological condition? Lancet. 1987 Oct 31;2(8566):996–999. doi: 10.1016/s0140-6736(87)92560-8. [DOI] [PubMed] [Google Scholar]
  10. Hayashi K., Eizuru Y., Sato S., Minamishima Y. The role of NK cell activity in age-dependent resistance of mice to murine cytomegalovirus infection. Microbiol Immunol. 1985;29(10):939–950. doi: 10.1111/j.1348-0421.1985.tb02958.x. [DOI] [PubMed] [Google Scholar]
  11. Hayashi K., Saze K., Uchida Y. Studies of latent cytomegalovirus infection: the macrophage as a virus-harboring cell. Microbiol Immunol. 1985;29(7):625–634. doi: 10.1111/j.1348-0421.1985.tb00866.x. [DOI] [PubMed] [Google Scholar]
  12. Ho M. Role of specific cytotoxic lymphocytes in cellular immunity against murine cytomegalovirus. Infect Immun. 1980 Mar;27(3):767–776. doi: 10.1128/iai.27.3.767-776.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jacobson M. A., Mills J. Serious cytomegalovirus disease in the acquired immunodeficiency syndrome (AIDS). Clinical findings, diagnosis, and treatment. Ann Intern Med. 1988 Apr;108(4):585–594. doi: 10.7326/0003-4819-108-4-585. [DOI] [PubMed] [Google Scholar]
  14. Laskin O. L., Stahl-Bayliss C. M., Morgello S. Concomitant herpes simplex virus type 1 and cytomegalovirus ventriculoencephalitis in acquired immunodeficiency syndrome. Arch Neurol. 1987 Aug;44(8):843–847. doi: 10.1001/archneur.1987.00520200047017. [DOI] [PubMed] [Google Scholar]
  15. MacGregor M. P., Lucia H. L., Vine W., FitzGerald P., Bia F. J. Effects of cyclosporine and cortisone on the pathogenesis of primary infection with cytomegalovirus in the guinea pig. J Infect Dis. 1986 Mar;153(3):503–510. doi: 10.1093/infdis/153.3.503. [DOI] [PubMed] [Google Scholar]
  16. Metselaar H. J., Velzing J., Rothbarth P. H., Balk A. H., Mochtar B., Weimar W. Prophylactic use of anti-CMV immunoglobulins in heart transplant recipients: a study on its safety. Transplant Proc. 1989 Feb;21(1 Pt 3):2504–2505. [PubMed] [Google Scholar]
  17. Murphy G. F., Brody A. R., Craighead J. E. Monocyte migration across pulmonary membranes in mice infected with cytomegalovirus. Exp Mol Pathol. 1975 Feb;22(1):35–44. doi: 10.1016/0014-4800(75)90049-0. [DOI] [PubMed] [Google Scholar]
  18. Reddehase M. J., Mutter W., Münch K., Bühring H. J., Koszinowski U. H. CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity. J Virol. 1987 Oct;61(10):3102–3108. doi: 10.1128/jvi.61.10.3102-3108.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reddehase M. J., Weiland F., Münch K., Jonjic S., Lüske A., Koszinowski U. H. Interstitial murine cytomegalovirus pneumonia after irradiation: characterization of cells that limit viral replication during established infection of the lungs. J Virol. 1985 Aug;55(2):264–273. doi: 10.1128/jvi.55.2.264-273.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. STERN H., ELEK S. D. THE INCIDENCE OF INFECTION WITH CYTOMEGALOVIRUS IN A NORMAL POPULATION. A SEROLOGICAL STUDY IN GREATER LONDON. J Hyg (Lond) 1965 Mar;63:79–87. doi: 10.1017/s0022172400044983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sarmiento M., Glasebrook A. L., Fitch F. W. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed] [Google Scholar]
  22. Selgrade M. K., Daniels M. J., Hu P. C., Miller F. J., Graham J. A. Effects of immunosuppression with cyclophosphamide on acute murine cytomegalovirus infection and virus-augmented natural killer cell activity. Infect Immun. 1982 Dec;38(3):1046–1055. doi: 10.1128/iai.38.3.1046-1055.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shanley J. D., Jordan M. C., Stevens J. G. Modification by adoptive humoral immunity of murine cytomegalovirus infection. J Infect Dis. 1981 Feb;143(2):231–237. doi: 10.1093/infdis/143.2.231. [DOI] [PubMed] [Google Scholar]
  24. Shanley J. D., Pesanti E. L. The relation of viral replication to interstitial pneumonitis in murine cytomegalovirus lung infection. J Infect Dis. 1985 Mar;151(3):454–458. doi: 10.1093/infdis/151.3.454. [DOI] [PubMed] [Google Scholar]
  25. Sriram S., Carroll L., Fortin S., Cooper S., Ranges G. In vivo immunomodulation by monoclonal anti-CD4 antibody. II. Effect on T cell response to myelin basic protein and experimental allergic encephalomyelitis. J Immunol. 1988 Jul 15;141(2):464–468. [PubMed] [Google Scholar]
  26. Swain S. L., Dialynas D. P., Fitch F. W., English M. Monoclonal antibody to L3T4 blocks the function of T cells specific for class 2 major histocompatibility complex antigens. J Immunol. 1984 Mar;132(3):1118–1123. [PubMed] [Google Scholar]
  27. Tegtmeyer P. J., Craighead J. E. Infection of adult mouse macrophages in vitro with cytomegalovirus. Proc Soc Exp Biol Med. 1968 Dec;129(3):690–694. doi: 10.3181/00379727-129-33399. [DOI] [PubMed] [Google Scholar]
  28. Watson J. G. Problems of infection after bone marrow transplantation. J Clin Pathol. 1983 Jun;36(6):683–692. doi: 10.1136/jcp.36.6.683. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES