This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jooss, K.
Right arrow Articles by Wilson, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jooss, K.
Right arrow Articles by Wilson, J. M.

 Previous Article  |  Next Article 

J Virol, April 1998, p. 2945-2954, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Cytotoxic T-Lymphocyte Target Proteins and Their Major Histocompatibility Complex Class I Restriction in Response to Adenovirus Vectors Delivered to Mouse Liver

Karin Jooss, Hildegund C. J. Ertl, and James M. Wilson*

Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania, and Wistar Institute, Philadelphia, Pennsylvania 19104

Received 19 November 1997/Accepted 23 December 1997

The activation of cytotoxic T lymphocytes (CTLs) to cells infected with adenovirus vectors contributes to problems of inflammation and transient gene expression that attend their use in gene therapy. The goal of this study was to identify in a murine model of liver gene therapy the proteins that provide targets to CTLs and to characterize the major histocompatibility complex (MHC) class I restricting elements. Mice of different MHC haplotypes were infected with an E1-deleted adenovirus expressing human alkaline phosphatase (ALP) or beta -galactosidase as a reporter protein, and splenocytes were harvested for in vitro CTL assays to aid in the characterization of CTL epitopes. A library of vaccinia viruses was created to express individual viral open reading frames, as well as the ALP and lacZ transgenes. The MHC haplotype had a dramatic impact on the distribution of CTL targets: in C57BL/6 mice, the hexon protein presented by both H-2Kb and H2Db was dominant, and in C3H mice, H-2Dk-restricted presentation of ALP was dominant. Adoptive transfer of CTLs specific for various adenovirus proteins or transgene products into either Rag-I or C3H-scid mice infected previously with an E1-deleted adenovirus verified the in vivo relevance of the adenovirus-specific CTL targets identified in vitro. The results of these experiments illustrate the impact of lr gene control on the response to gene therapy with adenovirus vectors and suggest that the efficacy of therapy with adenovirus vectors may exhibit considerable heterogeneity when applied in human populations.

* Corresponding author. Mailing address: 204 Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104-4268. Phone: (215) 898-3000. Fax: (215) 898-6588.




This article has been cited by other articles:

  • Joshi, A., Tang, J., Kuzma, M., Wagner, J., Mookerjee, B., Filicko, J., Carabasi, M., Flomenberg, N., Flomenberg, P. (2009). Adenovirus DNA polymerase is recognized by human CD8+ T cells. J. Gen. Virol. 90: 84-94 [Abstract] [Full Text]  
  • Krause, A., Joh, J. H., Hackett, N. R., Roelvink, P. W., Bruder, J. T., Wickham, T. J., Kovesdi, I., Crystal, R. G., Worgall, S. (2006). Epitopes expressed in different adenovirus capsid proteins induce different levels of epitope-specific immunity.. J. Virol. 80: 5523-5530 [Abstract] [Full Text]  
  • Li, X.-P., Li, C. Y.S., Li, X., Ding, Y., Chan, L. L.Y., Yang, P.-H., Li, G., Liu, X., Lin, J. S., Wang, J., He, M., Kung, H.-f., Lin, M. C., Peng, Y. (2006). Inhibition of human nasopharyngeal carcinoma growth and metastasis in mice by adenovirus-associated virus-mediated expression of human endostatin. Molecular Cancer Therapeutics 5: 1290-1298 [Abstract] [Full Text]  
  • Dobrzynski, E., Fitzgerald, J. C., Cao, O., Mingozzi, F., Wang, L., Herzog, R. W. (2006). Prevention of cytotoxic T lymphocyte responses to factor IX-expressing hepatocytes by gene transfer-induced regulatory T cells. Proc. Natl. Acad. Sci. USA 103: 4592-4597 [Abstract] [Full Text]  
  • Park, J. M., Terabe, M., Sakai, Y., Munasinghe, J., Forni, G., Morris, J. C., Berzofsky, J. A. (2005). Early Role of CD4+ Th1 Cells and Antibodies in HER-2 Adenovirus Vaccine Protection against Autochthonous Mammary Carcinomas. J. Immunol. 174: 4228-4236 [Abstract] [Full Text]  
  • Muruve, D. A., Cotter, M. J., Zaiss, A. K., White, L. R., Liu, Q., Chan, T., Clark, S. A., Ross, P. J., Meulenbroek, R. A., Maelandsmo, G. M., Parks, R. J. (2004). Helper-Dependent Adenovirus Vectors Elicit Intact Innate but Attenuated Adaptive Host Immune Responses In Vivo. J. Virol. 78: 5966-5972 [Abstract] [Full Text]  
  • Sumida, S. M., Truitt, D. M., Kishko, M. G., Arthur, J. C., Jackson, S. S., Gorgone, D. A., Lifton, M. A., Koudstaal, W., Pau, M. G., Kostense, S., Havenga, M. J. E., Goudsmit, J., Letvin, N. L., Barouch, D. H. (2004). Neutralizing Antibodies and CD8+ T Lymphocytes both Contribute to Immunity to Adenovirus Serotype 5 Vaccine Vectors. J. Virol. 78: 2666-2673 [Abstract] [Full Text]  
  • Yang, T. C., Dayball, K., Wan, Y. H., Bramson, J. (2003). Detailed Analysis of the CD8+ T-Cell Response following Adenovirus Vaccination. J. Virol. 77: 13407-13411 [Abstract] [Full Text]  
  • Wiethe, C., Dittmar, K., Doan, T., Lindenmaier, W., Tindle, R. (2003). Provision of 4-1BB Ligand Enhances Effector and Memory CTL Responses Generated by Immunization with Dendritic Cells Expressing a Human Tumor-Associated Antigen. J. Immunol. 170: 2912-2922 [Abstract] [Full Text]  
  • Varnavski, A. N., Zhang, Y., Schnell, M., Tazelaar, J., Louboutin, J.-P., Yu, Q.-C., Bagg, A., Gao, G.-p., Wilson, J. M. (2002). Preexisting Immunity to Adenovirus in Rhesus Monkeys Fails To Prevent Vector-Induced Toxicity. J. Virol. 76: 5711-5719 [Abstract] [Full Text]  
  • Thomas, C. E., Edwards, P., Wickham, T. J., Castro, M. G., Lowenstein, P. R. (2002). Adenovirus Binding to the Coxsackievirus and Adenovirus Receptor or Integrins Is Not Required To Elicit Brain Inflammation but Is Necessary To Transduce Specific Neural Cell Types. J. Virol. 76: 3452-3460 [Abstract] [Full Text]  
  • Mercier, S., Gahery-Segard, H., Monteil, M., Lengagne, R., Guillet, J.-G., Eloit, M., Denesvre, C. (2002). Distinct Roles of Adenovirus Vector-Transduced Dendritic Cells, Myoblasts, and Endothelial Cells in Mediating an Immune Response against a Transgene Product. J. Virol. 76: 2899-2911 [Abstract] [Full Text]  
  • Molinier-Frenkel, V., Lengagne, R., Gaden, F., Hong, S.-S., Choppin, J., Gahery-Segard, H., Boulanger, P., Guillet, J.-G. (2002). Adenovirus Hexon Protein Is a Potent Adjuvant for Activation of a Cellular Immune Response. J. Virol. 76: 127-135 [Abstract] [Full Text]  
  • Sun, J., Bodola, F., Fan, X., Irshad, H., Soong, L., Lemon, S. M., Chan, T.-S. (2001). Hepatitis C Virus Core and Envelope Proteins Do Not Suppress the Host's Ability To Clear a Hepatic Viral Infection. J. Virol. 75: 11992-11998 [Abstract] [Full Text]  
  • Zoltick, P. W., Chirmule, N., Schnell, M. A., Gao, G.-P., Hughes, J. V., Wilson, J. M. (2001). Biology of E1-Deleted Adenovirus Vectors in Nonhuman Primate Muscle. J. Virol. 75: 5222-5229 [Abstract] [Full Text]  
  • Croyle, M. A., Chirmule, N., Zhang, Y., Wilson, J. M. (2001). "Stealth" Adenoviruses Blunt Cell-Mediated and Humoral Immune Responses against the Virus and Allow for Significant Gene Expression upon Readministration in the Lung. J. Virol. 75: 4792-4801 [Abstract] [Full Text]  
  • Liu, Z.-X., Govindarajan, S., Okamoto, S., Dennert, G. (2001). Fas-Mediated Apoptosis Causes Elimination of Virus-Specific Cytotoxic T Cells in the Virus-Infected Liver. J. Immunol. 166: 3035-3041 [Abstract] [Full Text]  
  • Sarukhan, A., Camugli, S., Gjata, B., von Boehmer, H., Danos, O., Jooss, K. (2001). Successful Interference with Cellular Immune Responses to Immunogenic Proteins Encoded by Recombinant Viral Vectors. J. Virol. 75: 269-277 [Abstract] [Full Text]  
  • Russell, W. C. (2000). Update on adenovirus and its vectors. J. Gen. Virol. 81: 2573-2604 [Full Text]  
  • Allamand, V., Campbell, K. P. (2000). Animal models for muscular dystrophy: valuable tools for the development of therapies. Hum Mol Genet 9: 2459-2467 [Abstract] [Full Text]  
  • Molinier-Frenkel, V., Gahery-Segard, H., Mehtali, M., Le Boulaire, C., Ribault, S., Boulanger, P., Tursz, T., Guillet, J.-G., Farace, F. (2000). Immune Response to Recombinant Adenovirus in Humans: Capsid Components from Viral Input Are Targets for Vector-Specific Cytotoxic T Lymphocytes. J. Virol. 74: 7678-7682 [Abstract] [Full Text]  
  • Liu, Z.-X., Govindarajan, S., Okamoto, S., Dennert, G. (2000). NK Cells Cause Liver Injury and Facilitate the Induction of T Cell-Mediated Immunity to a Viral Liver Infection. J. Immunol. 164: 6480-6486 [Abstract] [Full Text]  
  • Lozier, J. N., Metzger, M. E., Donahue, R. E., Morgan, R. A. (1999). Adenovirus-Mediated Expression of Human Coagulation Factor IX in the Rhesus Macaque Is Associated With Dose-Limiting Toxicity. Blood 94: 3968-3975 [Abstract] [Full Text]  
  • Gorziglia, M. I., Lapcevich, C., Roy, S., Kang, Q., Kadan, M., Wu, V., Pechan, P., Kaleko, M. (1999). Generation of an Adenovirus Vector Lacking E1, E2a, E3, and All of E4 except Open Reading Frame 3. J. Virol. 73: 6048-6055 [Abstract] [Full Text]  
  • Kaplan, J. M., Armentano, D., Scaria, A., Woodworth, L. A., Pennington, S. E., Wadsworth, S. C., Smith, A. E., Gregory, R. J. (1999). Novel Role for E4 Region Genes in Protection of Adenovirus Vectors from Lysis by Cytotoxic T Lymphocytes. J. Virol. 73: 4489-4492 [Abstract] [Full Text]  
  • Stein, C. S., Ghodsi, A., Derksen, T., Davidson, B. L. (1999). Systemic and Central Nervous System Correction of Lysosomal Storage in Mucopolysaccharidosis Type VII Mice. J. Virol. 73: 3424-3429 [Abstract] [Full Text]  
  • Moorhead, J. W., Clayton, G. H., Smith, R. L., Schaack, J. (1999). A Replication-Incompetent Adenovirus Vector with the Preterminal Protein Gene Deleted Efficiently Transduces Mouse Ears. J. Virol. 73: 1046-1053 [Abstract] [Full Text]  
  • Jooss, K., Gjata, B., Danos, O., von Boehmer, H., Sarukhan, A. (2001). Regulatory function of in vivo anergized CD4+ T cells. Proc. Natl. Acad. Sci. USA 98: 8738-8743 [Abstract] [Full Text]  
  • Qian, H. S., Channon, K., Neplioueva, V., Wang, Q., Finer, M., Tsui, L., George, S. E., McArthur, J. (2001). Improved Adenoviral Vector for Vascular Gene Therapy : Beneficial Effects on Vascular Function and Inflammation. Circ. Res. 88: 911-917 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»