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 Zarozinski, C. C.
Right arrow Articles by Welsh, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zarozinski, C. C.
Right arrow Articles by Welsh, R. M.

 Previous Article  |  Next Article 

Journal of Virology, April 2000, p. 3650-3658, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Bystander Sensitization to Activation-Induced Cell Death as a Mechanism of Virus-Induced Immune Suppression

Christopher C. Zarozinski,dagger James M. McNally, Barbara L. Lohman,Dagger Keith A. Daniels, and Raymond M. Welsh*

Department of Pathology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655

Received 18 October 1999/Accepted 18 January 2000

Viral infections which induce strong T-cell responses are often characterized by a period of transient immunodeficiency associated with the failure of host T cells to proliferate in response to mitogens or to mount memory recall responses to other antigens. During acute infections, most of the activated, proliferating virus-specific T cells are sensitized to undergo apoptosis on strong T-cell receptor (TCR) stimulation, but it has not been known why memory T cells not specific for the virus fail to proliferate on exposure to their cognate antigen. Using a lymphocytic choriomeningitis virus (LCMV) infection model in which LCMV-immune Thy 1.1+ splenocytes are adoptively transferred into Thy 1.2+ LCMV carrier mice, we demonstrate here that T cells clearly defined as not specific for the virus are sensitized to undergo activation-induced cell death on TCR stimulation in vitro. This bystander sensitization was in part dependent on the expression of Fas ligand (FasL) on the activated virus-specific cells and gamma interferon (IFN-gamma ) receptor expression on the bystander T cells. We propose that FasL from highly activated antiviral T cells may sensitize IFN-gamma -conditioned T cells not specific for the virus to undergo apoptosis rather than to proliferate on encountering antigen. This may in part explain the failure of memory T cells to respond to recall antigens during acute and persistent viral infections.


* Corresponding author. Mailing address: Department of Pathology, University of Massachusetts Medical Center, 55 Lake Ave. North, Worcester, MA 01655. Phone: (508) 856-5819. Fax: (508) 856-5780. E-mail: raymond.welsh{at}umassmed.edu.

dagger Present address: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02155.

Dagger Present address: California Regional Primate Research Center, University of California, Davis, CA 95615.


Journal of Virology, April 2000, p. 3650-3658, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Inaba, H., Geiger, T. L. (2006). Defective cell cycle induction by IL-2 in naive T-cells antigen stimulated in the presence of refractory T-lymphocytes. Int Immunol 18: 1043-1054 [Abstract] [Full Text]  
  • Perez, S., Inman, M., Doster, A., Jones, C. (2005). Latency-Related Gene Encoded by Bovine Herpesvirus 1 Promotes Virus Growth and Reactivation from Latency in Tonsils of Infected Calves. J. Clin. Microbiol. 43: 393-401 [Abstract] [Full Text]  
  • Hirsch, V. M., Santra, S., Goldstein, S., Plishka, R., Buckler-White, A., Seth, A., Ourmanov, I., Brown, C. R., Engle, R., Montefiori, D., Glowczwskie, J., Kunstman, K., Wolinsky, S., Letvin, N. L. (2004). Immune Failure in the Absence of Profound CD4+ T-Lymphocyte Depletion in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques. J. Virol. 78: 275-284 [Abstract] [Full Text]  
  • Suvas, S., Kumaraguru, U., Pack, C. D., Lee, S., Rouse, B. T. (2003). CD4+CD25+ T Cells Regulate Virus-specific Primary and Memory CD8+ T Cell Responses. JEM 198: 889-901 [Abstract] [Full Text]  
  • Sieling, P. A., Chung, W., Duong, B. T., Godowski, P. J., Modlin, R. L. (2003). Toll-Like Receptor 2 Ligands as Adjuvants for Human Th1 Responses. J. Immunol. 170: 194-200 [Abstract] [Full Text]  
  • Ryon, J. J., Moss, W. J., Monze, M., Griffin, D. E. (2002). Functional and Phenotypic Changes in Circulating Lymphocytes from Hospitalized Zambian Children with Measles. CVI 9: 994-1003 [Abstract] [Full Text]  
  • Topham, D. J., Castrucci, M. R., Wingo, F. S., Belz, G. T., Doherty, P. C. (2001). The Role of Antigen in the Localization of Naive, Acutely Activated, and Memory CD8+ T Cells to the Lung During Influenza Pneumonia. J. Immunol. 167: 6983-6990 [Abstract] [Full Text]  
  • Hobbs, J. A., Cho, S., Roberts, T. J., Sriram, V., Zhang, J., Xu, M., Brutkiewicz, R. R. (2001). Selective Loss of Natural Killer T Cells by Apoptosis following Infection with Lymphocytic Choriomeningitis Virus. J. Virol. 75: 10746-10754 [Abstract] [Full Text]  
  • Lodolce, J. P., Burkett, P. R., Boone, D. L., Chien, M., Ma, A. (2001). T Cell-independent Interleukin 15R{alpha} Signals Are Required for Bystander Proliferation. JEM 194: 1187-1194 [Abstract] [Full Text]  
  • Wu-Hsieh, B. A., Whitmire, J. K., de Fries, R., Lin, J.-S., Matloubian, M., Ahmed, R. (2001). Distinct CD8 T Cell Functions Mediate Susceptibility to Histoplasmosis During Chronic Viral Infection. J. Immunol. 167: 4566-4573 [Abstract] [Full Text]  
  • McNally, J. M., Zarozinski, C. C., Lin, M.-Y., Brehm, M. A., Chen, H. D., Welsh, R. M. (2001). Attrition of Bystander CD8 T Cells during Virus-Induced T-Cell and Interferon Responses. J. Virol. 75: 5965-5976 [Abstract] [Full Text]