This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 Ganusov, V. V.
Right arrow Articles by De Boer, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ganusov, V. V.
Right arrow Articles by De Boer, R. J.

 Previous Article  |  Next Article 

Journal of Virology, December 2008, p. 11749-11757, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.01128-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Estimating In Vivo Death Rates of Targets due to CD8 T-Cell-Mediated Killing{triangledown} ,{dagger}

Vitaly V. Ganusov*{ddagger} and Rob J. De Boer

Theoretical Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands

Received 29 May 2008/ Accepted 16 September 2008

Despite recent advances in immunology, several key parameters determining virus dynamics in infected hosts remain largely unknown. For example, the rate at which specific effector and memory CD8 T cells clear virus-infected cells in vivo is hardly known for any viral infection. We propose a framework to quantify T-cell-mediated killing of infected or peptide-pulsed target cells using the widely used in vivo cytotoxicity assay. We have reanalyzed recently published data on killing of peptide-pulsed splenocytes by cytotoxic T lymphocytes and memory CD8 T cells specific to NP396 and GP276 epitopes of lymphocytic choriomeningitis virus (LCMV) in the mouse spleen. Because there are so many effector CD8 T cells in spleens of mice at the peak of the immune response, NP396- and GP276-pulsed targets are estimated to have very short half-lives of 2 and 14 min, respectively. After the effector numbers have diminished, i.e., in LCMV-immune mice, the half-lives become 48 min and 2.8 h for NP396- and GP276-expressing targets, respectively. Analysis of several alternative models demonstrates that the estimates of half-life times of peptide-pulsed targets are not affected when changes are made in the model assumptions. Our report provides a unifying framework to compare killing efficacies of CD8 T-cell responses specific to different viral and bacterial infections in vivo, which may be used to compare efficacies of various cytotoxic-T-lymphocyte-based vaccines.

* Corresponding author. Present address: Theoretical Biology and Biophysics, T-10 MS-K710, Los Alamos National Laboratory, Los Alamos, NM 87545. Phone: (505) 665-5120. Fax: (505) 665-3493. E-mail: vitaly.ganusov{at}gmail.com

{triangledown} Published ahead of print on 24 September 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} Permanent address: Institute of Biophysics and Krasnoyarsk Science Center, Siberian Branch of the Russian Academy of Sciences, Akademgorodok, Russia 660036.

Journal of Virology, December 2008, p. 11749-11757, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.01128-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Schiffer, J. T., Abu-Raddad, L., Mark, K. E., Zhu, J., Selke, S., Magaret, A., Wald, A., Corey, L. (2009). Frequent Release of Low Amounts of Herpes Simplex Virus from Neurons: Results of a Mathematical Model. Sci Transl Med 1: 7ra16-7ra16 [Abstract] [Full Text]  
  • Lee, H. Y., Topham, D. J., Park, S. Y., Hollenbaugh, J., Treanor, J., Mosmann, T. R., Jin, X., Ward, B. M., Miao, H., Holden-Wiltse, J., Perelson, A. S., Zand, M., Wu, H. (2009). Simulation and Prediction of the Adaptive Immune Response to Influenza A Virus Infection. J. Virol. 83: 7151-7165 [Abstract] [Full Text]  
  • Regner, M., Pavlinovic, L., Koskinen, A., Young, N., Trapani, J. A., Mullbacher, A. (2009). Cutting Edge: Rapid and Efficient In Vivo Cytotoxicity by Cytotoxic T Cells Is Independent of Granzymes A and B. J. Immunol. 183: 37-40 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»