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. 1994 Sep;94(3):1019–1025. doi: 10.1172/JCI117415

Murine cytomegalovirus-associated pneumonitis in the lungs free of the virus.

K Tanaka 1, Y Koga 1, Y Y Lu 1, X Y Zhang 1, Y Wang 1, G Kimura 1, K Nomoto 1
PMCID: PMC295152  PMID: 8083343

Abstract

At 4 wk after intraperitoneal inoculation of murine cytomegalovirus (MCMV) in adult BALB/c mice, MCMV remained detectable only in the salivary glands. When T cells of these mice were activated by a single injection of anti-CD3 epsilon monoclonal antibody, mice died of interstitial pneumonitis at 24-48 h after injection, accompanied by elevation of serum levels of TNF-alpha and IFN-gamma. However, MCMV remained undetectable in the lungs during the period. Simultaneous injection of cyclosporin A reduced such effects of anti-CD3. In conclusion, although the presence of MCMV in the host may be required, MCMV-associated pneumonitis is not mediated by virus in the lung but probably by the cytokines released from T cells, of which responsiveness to stimulation via CD3 molecule has been presumably modified by MCMV infection.

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Selected References

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

  1. Alegre M. L., Vandenabeele P., Depierreux M., Florquin S., Deschodt-Lanckman M., Flamand V., Moser M., Leo O., Urbain J., Fiers W. Cytokine release syndrome induced by the 145-2C11 anti-CD3 monoclonal antibody in mice: prevention by high doses of methylprednisolone. J Immunol. 1991 Feb 15;146(4):1184–1191. [PubMed] [Google Scholar]
  2. Balthesen M., Messerle M., Reddehase M. J. Lungs are a major organ site of cytomegalovirus latency and recurrence. J Virol. 1993 Sep;67(9):5360–5366. doi: 10.1128/jvi.67.9.5360-5366.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Broaddus C., Dake M. D., Stulbarg M. S., Blumenfeld W., Hadley W. K., Golden J. A., Hopewell P. C. Bronchoalveolar lavage and transbronchial biopsy for the diagnosis of pulmonary infections in the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Jun;102(6):747–752. doi: 10.7326/0003-4819-102-6-747. [DOI] [PubMed] [Google Scholar]
  4. Carding S. R., Allan W., McMickle A., Doherty P. C. Activation of cytokine genes in T cells during primary and secondary murine influenza pneumonia. J Exp Med. 1993 Feb 1;177(2):475–482. doi: 10.1084/jem.177.2.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chatenoud L., Ferran C., Reuter A., Legendre C., Gevaert Y., Kreis H., Franchimont P., Bach J. F. Systemic reaction to the anti-T-cell monoclonal antibody OKT3 in relation to serum levels of tumor necrosis factor and interferon-gamma [corrected]. N Engl J Med. 1989 May 25;320(21):1420–1421. doi: 10.1056/NEJM198905253202117. [DOI] [PubMed] [Google Scholar]
  6. Dudding L., Haskill S., Clark B. D., Auron P. E., Sporn S., Huang E. S. Cytomegalovirus infection stimulates expression of monocyte-associated mediator genes. J Immunol. 1989 Nov 15;143(10):3343–3352. [PubMed] [Google Scholar]
  7. Forman S. J. Clinical insights and observations contributing to the understanding of cytomegalovirus disease pathogenesis. Bone marrow transplantation. Transplant Proc. 1991 Jun;23(3 Suppl 3):110-4, discussion 114. [PubMed] [Google Scholar]
  8. Gallant J. E., Moore R. D., Richman D. D., Keruly J., Chaisson R. E. Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group. J Infect Dis. 1992 Dec;166(6):1223–1227. doi: 10.1093/infdis/166.6.1223. [DOI] [PubMed] [Google Scholar]
  9. Gong J. H., Sprenger H., Hinder F., Bender A., Schmidt A., Horch S., Nain M., Gemsa D. Influenza A virus infection of macrophages. Enhanced tumor necrosis factor-alpha (TNF-alpha) gene expression and lipopolysaccharide-triggered TNF-alpha release. J Immunol. 1991 Nov 15;147(10):3507–3513. [PubMed] [Google Scholar]
  10. 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]
  11. Grundy J. E., Shanley J. D., Shearer G. M. Augmentation of graft-versus-host reaction by cytomegalovirus infection resulting in interstitial pneumonitis. Transplantation. 1985 May;39(5):548–553. doi: 10.1097/00007890-198505000-00018. [DOI] [PubMed] [Google Scholar]
  12. Henke A., Mohr C., Sprenger H., Graebner C., Stelzner A., Nain M., Gemsa D. Coxsackievirus B3-induced production of tumor necrosis factor-alpha, IL-1 beta, and IL-6 in human monocytes. J Immunol. 1992 Apr 1;148(7):2270–2277. [PubMed] [Google Scholar]
  13. Hirsch R., Gress R. E., Pluznik D. H., Eckhaus M., Bluestone J. A. Effects of in vivo administration of anti-CD3 monoclonal antibody on T cell function in mice. II. In vivo activation of T cells. J Immunol. 1989 Feb 1;142(3):737–743. [PubMed] [Google Scholar]
  14. Hudson J. B. The murine cytomegalovirus as a model for the study of viral pathogenesis and persistent infections. Arch Virol. 1979;62(1):1–29. doi: 10.1007/BF01314900. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Kahan B. D. Cyclosporine. N Engl J Med. 1989 Dec 21;321(25):1725–1738. doi: 10.1056/NEJM198912213212507. [DOI] [PubMed] [Google Scholar]
  17. Keil G. M., Ebeling-Keil A., Koszinowski U. H. Immediate-early genes of murine cytomegalovirus: location, transcripts, and translation products. J Virol. 1987 Feb;61(2):526–533. doi: 10.1128/jvi.61.2.526-533.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Keil G. M., Ebeling-Keil A., Koszinowski U. H. Sequence and structural organization of murine cytomegalovirus immediate-early gene 1. J Virol. 1987 Jun;61(6):1901–1908. doi: 10.1128/jvi.61.6.1901-1908.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koga Y., Tanaka K., Lu Y. Y., Oh-Tsu M., Sasaki M., Kimura G., Nomoto K. Priming of immature thymocytes to CD3-mediated apoptosis by infection with murine cytomegalovirus. J Virol. 1994 Jul;68(7):4322–4328. doi: 10.1128/jvi.68.7.4322-4328.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pass H. I., Potter D. A., Macher A. M., Reichert C., Shelhammer J. H., Masur H., Ognibene F., Gelmann E., Lane H. C., Fauci A. Thoracic manifestations of the acquired immune deficiency syndrome. J Thorac Cardiovasc Surg. 1984 Nov;88(5 Pt 1):654–658. [PubMed] [Google Scholar]
  21. Piguet P. F., Collart M. A., Grau G. E., Sappino A. P., Vassalli P. Requirement of tumour necrosis factor for development of silica-induced pulmonary fibrosis. Nature. 1990 Mar 15;344(6263):245–247. doi: 10.1038/344245a0. [DOI] [PubMed] [Google Scholar]
  22. Pomeroy C., Hilleren P. J., Jordan M. C. Latent murine cytomegalovirus DNA in splenic stromal cells of mice. J Virol. 1991 Jun;65(6):3330–3334. doi: 10.1128/jvi.65.6.3330-3334.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Quinnan G. V., Jr, Masur H., Rook A. H., Armstrong G., Frederick W. R., Epstein J., Manischewitz J. F., Macher A. M., Jackson L., Ames J. Herpesvirus infections in the acquired immune deficiency syndrome. JAMA. 1984 Jul 6;252(1):72–77. [PubMed] [Google Scholar]
  24. Reed E. C., Dandliker P. S., Meyers J. D. Treatment of cytomegalovirus pneumonia with 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine and high-dose corticosteroids. Ann Intern Med. 1986 Aug;105(2):214–215. doi: 10.7326/0003-4819-105-2-214. [DOI] [PubMed] [Google Scholar]
  25. Reichert C. M., O'Leary T. J., Levens D. L., Simrell C. R., Macher A. M. Autopsy pathology in the acquired immune deficiency syndrome. Am J Pathol. 1983 Sep;112(3):357–382. [PMC free article] [PubMed] [Google Scholar]
  26. Schmidt G. M., Horak D. A., Niland J. C., Duncan S. R., Forman S. J., Zaia J. A. A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants; The City of Hope-Stanford-Syntex CMV Study Group. N Engl J Med. 1991 Apr 11;324(15):1005–1011. doi: 10.1056/NEJM199104113241501. [DOI] [PubMed] [Google Scholar]
  27. Shanley J. D., Pesanti E. L., Nugent K. M. The pathogenesis of pneumonitis due to murine cytomegalovirus. J Infect Dis. 1982 Sep;146(3):388–396. doi: 10.1093/infdis/146.3.388. [DOI] [PubMed] [Google Scholar]
  28. Shepp D. H., Dandliker P. S., de Miranda P., Burnette T. C., Cederberg D. M., Kirk L. E., Meyers J. D. Activity of 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine in the treatment of cytomegalovirus pneumonia. Ann Intern Med. 1985 Sep;103(3):368–373. doi: 10.7326/0003-4819-103-3-368. [DOI] [PubMed] [Google Scholar]
  29. Smith P. D., Saini S. S., Raffeld M., Manischewitz J. F., Wahl S. M. Cytomegalovirus induction of tumor necrosis factor-alpha by human monocytes and mucosal macrophages. J Clin Invest. 1992 Nov;90(5):1642–1648. doi: 10.1172/JCI116035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Stover D. E., Zaman M. B., Hajdu S. I., Lange M., Gold J., Armstrong D. Bronchoalveolar lavage in the diagnosis of diffuse pulmonary infiltrates in the immunosuppressed host. Ann Intern Med. 1984 Jul;101(1):1–7. doi: 10.7326/0003-4819-101-1-1. [DOI] [PubMed] [Google Scholar]
  31. Tanaka K., Koga Y., Zhang X. Y., Sasaki M., Wang Y., Kimura G., Nomoto K. Extensive apoptosis occurring in the thymus during accelerated rejection of cardiac allografts in presensitized rats. J Immunol. 1993 Jul 15;151(2):748–758. [PubMed] [Google Scholar]
  32. Zaia J. A. Pathogenesis of CMV-associated diseases in 1990. Transplant Proc. 1991 Jun;23(3 Suppl 3):1–4. [PubMed] [Google Scholar]

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