Previous Article | Next Article 
Journal of Virology, August 2000, p. 7496-7507, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Murine Model of Interstitial Cytomegalovirus
Pneumonia in Syngeneic Bone Marrow Transplantation: Persistence of
Protective Pulmonary CD8-T-Cell Infiltrates after Clearance of
Acute Infection
Jürgen
Podlech,
Rafaela
Holtappels,
Marcus-Folker
Pahl-Seibert,
Hans-Peter
Steffens,
and
Matthias J.
Reddehase*
Institute for Virology, Johannes Gutenberg
University, Hochhaus am Augustusplatz, 55101 Mainz, Germany
Received 21 March 2000/Accepted 22 May 2000
Interstitial pneumonia (IP) is a severe organ manifestation of
cytomegalovirus (CMV) disease in the immunocompromised host, in
particular in recipients of bone marrow transplantation (BMT). Diagnostic criteria for the definition of CMV-IP include clinical evidence of pneumonia together with CMV detected in bronchoalveolar lavage or lung biopsy. We have used the model of syngeneic BMT and
simultaneous infection of BALB/c mice with murine CMV for studying the
pathogenesis of CMV-IP by controlled longitudinal analysis. A
disseminated cytopathic infection of the lungs with fatal outcome was
observed only when reconstituting CD8 T cells were depleted. Neither
CD8 nor CD4 T cells mediated an immunopathogenesis of acute CMV-IP. By
contrast, after efficient hematolymphopoietic reconstitution, viral
replication in the lungs was moderate and focal. The histopathological
picture was dominated by preferential infiltration of CD8 T cells
confining viral replication to inflammatory foci. Notably, after
clearance of acute infection, CD62Llo and
CD62Lhi subsets of CD44+ memory CD8 T cells
were found to persist in lung tissue. One can thus operationally
distinguish an early CMV-positive IP (phase 1) and a late CMV-negative
IP (phase 2). According to the definition, phase 2 histopathology would
not be diagnosed as a CMV-IP and could instead be misinterpreted as a
CMV-induced immunopathology. We document here that phase 1 as well as
phase 2 pulmonary CD8 T cells are capable of exerting effector
functions and are effectual in protecting against productive infection.
We propose that antiviral "stand-by" memory-effector T cells
persist in the lungs to prevent virus recurrence from latency.
*
Corresponding author. Mailing address: Institute for
Virology, Johannes Gutenberg University, Hochhaus am Augustusplatz,
55101 Mainz, Germany. Phone: 49-6131-39-33650. Fax: 49-6131-39-35604. E-mail: Matthias.Reddehase{at}uni-mainz.de.

Present address: Miltenyi Biotec GmbH, 51429 Bergisch-Gladbach,
Germany.
Journal of Virology, August 2000, p. 7496-7507, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Bohm, V., Seckert, C. K., Simon, C. O., Thomas, D., Renzaho, A., Gendig, D., Holtappels, R., Reddehase, M. J.
(2009). Immune Evasion Proteins Enhance Cytomegalovirus Latency in the Lungs. J. Virol.
83: 10293-10298
[Abstract]
[Full Text]
-
Bantug, G. R. B., Cekinovic, D., Bradford, R., Koontz, T., Jonjic, S., Britt, W. J.
(2008). CD8+ T Lymphocytes Control Murine Cytomegalovirus Replication in the Central Nervous System of Newborn Animals. J. Immunol.
181: 2111-2123
[Abstract]
[Full Text]
-
Lang, A., Brien, J. D., Messaoudi, I., Nikolich-Zugich, J.
(2008). Age-Related Dysregulation of CD8+ T Cell Memory Specific for a Persistent Virus Is Independent of Viral Replication. J. Immunol.
180: 4848-4857
[Abstract]
[Full Text]
-
Tanaka, K., Sawamura, S., Satoh, T., Kobayashi, K., Noda, S.
(2007). Role of the Indigenous Microbiota in Maintaining the Virus-Specific CD8 Memory T Cells in the Lung of Mice Infected with Murine Cytomegalovirus. J. Immunol.
178: 5209-5216
[Abstract]
[Full Text]
-
Simon, C. O., Holtappels, R., Tervo, H.-M., Bohm, V., Daubner, T., Oehrlein-Karpi, S. A., Kuhnapfel, B., Renzaho, A., Strand, D., Podlech, J., Reddehase, M. J., Grzimek, N. K. A.
(2006). CD8 T Cells Control Cytomegalovirus Latency by Epitope-Specific Sensing of Transcriptional Reactivation. J. Virol.
80: 10436-10456
[Abstract]
[Full Text]
-
Erlach, K. C., Bohm, V., Seckert, C. K., Reddehase, M. J., Podlech, J.
(2006). Lymphoma cell apoptosis in the liver induced by distant murine cytomegalovirus infection.. J. Virol.
80: 4801-4819
[Abstract]
[Full Text]
-
Pahl-Seibert, M.-F., Juelch, M., Podlech, J., Thomas, D., Deegen, P., Reddehase, M. J., Holtappels, R.
(2005). Highly Protective In Vivo Function of Cytomegalovirus IE1 Epitope-Specific Memory CD8 T Cells Purified by T-Cell Receptor-Based Cell Sorting. J. Virol.
79: 5400-5413
[Abstract]
[Full Text]
-
Simon, C. O., Seckert, C. K., Dreis, D., Reddehase, M. J., Grzimek, N. K. A.
(2005). Role for Tumor Necrosis Factor Alpha in Murine Cytomegalovirus Transcriptional Reactivation in Latently Infected Lungs. J. Virol.
79: 326-340
[Abstract]
[Full Text]
-
Beutler, T., Hoflich, C., Stevens, P. A., Kruger, D. H., Prosch, S.
(2003). Downregulation of the Epidermal Growth Factor Receptor by Human Cytomegalovirus Infection in Human Fetal Lung Fibroblasts. Am. J. Respir. Cell Mol. Bio.
28: 86-94
[Abstract]
[Full Text]
-
Holtappels, R., Grzimek, N. K. A., Simon, C. O., Thomas, D., Dreis, D., Reddehase, M. J.
(2002). Processing and Presentation of Murine Cytomegalovirus pORFm164-Derived Peptide in Fibroblasts in the Face of All Viral Immunosubversive Early Gene Functions. J. Virol.
76: 6044-6053
[Abstract]
[Full Text]
-
Erlach, K. C., Podlech, J., Rojan, A., Reddehase, M. J.
(2002). Tumor Control in a Model of Bone Marrow Transplantation and Acute Liver-Infiltrating B-Cell Lymphoma: an Unpredicted Novel Function of Cytomegalovirus. J. Virol.
76: 2857-2870
[Abstract]
[Full Text]
-
Holtappels, R., Thomas, D., Podlech, J., Reddehase, M. J.
(2002). Two Antigenic Peptides from Genes m123 and m164 of Murine Cytomegalovirus Quantitatively Dominate CD8 T-Cell Memory in the H-2d Haplotype. J. Virol.
76: 151-164
[Abstract]
[Full Text]
-
Holtappels, R., Podlech, J., Grzimek, N. K. A., Thomas, D., Pahl-Seibert, M.-F., Reddehase, M. J.
(2001). Experimental Preemptive Immunotherapy of Murine Cytomegalovirus Disease with CD8 T-Cell Lines Specific for ppM83 and pM84, the Two Homologs of Human Cytomegalovirus Tegument Protein ppUL83 (pp65). J. Virol.
75: 6584-6600
[Abstract]
[Full Text]
-
Grzimek, N. K. A., Dreis, D., Schmalz, S., Reddehase, M. J.
(2001). Random, Asynchronous, and Asymmetric Transcriptional Activity of Enhancer-Flanking Major Immediate-Early Genes ie1/3 and ie2 during Murine Cytomegalovirus Latency in the Lungs. J. Virol.
75: 2692-2705
[Abstract]
[Full Text]
-
Holtappels, R., Pahl-Seibert, M.-F., Thomas, D., Reddehase, M. J.
(2000). Enrichment of Immediate-Early 1 (m123/pp89) Peptide-Specific CD8 T Cells in a Pulmonary CD62Llo Memory-Effector Cell Pool during Latent Murine Cytomegalovirus Infection of the Lungs. J. Virol.
74: 11495-11503
[Abstract]
[Full Text]
-
Wang, Z., Zheng, T., Zhu, Z., Homer, R. J., Riese, R. J., Chapman, H. A. Jr., Shapiro, S. D., Elias, J. A.
(2000). Interferon {gamma} Induction of Pulmonary Emphysema in the Adult Murine Lung. JEM
192: 1587-1600
[Abstract]
[Full Text]