Skip Navigation


International Immunology Advance Access originally published online on August 15, 2005
International Immunology 2005 17(9):1269-1276; doi:10.1093/intimm/dxh303
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
17/9/1269    most recent
dxh303v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (4)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Wodarz, D.
Right arrow Articles by Thomsen, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wodarz, D.
Right arrow Articles by Thomsen, A. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

Effect of the CTL proliferation program on virus dynamics

Dominik Wodarz1 and Allan Randrup Thomsen2

1 Department of Ecology and Evolutionary Biology, 321 Steinhaus Hall, University of California, Irvine, CA 92697, USA
2 Institute of Medical Microbiology and Immunology, Panum Institute, University of Copenhagen, Building 22.5.16, 3C Blegdamsvej, DK-2200 Copenhagen, Denmark

Correspondence to: D. Wodarz; E-mail: dwodarz{at}uci.edu

Experiments have established that CTLs do not require continuous antigenic stimulation for expansion. Instead, responses develop by a process of programmed proliferation which involves ~7–10 antigen-independent cell divisions, the generation of effector cells and the differentiation into memory cells. The effect of this program on the infection dynamics and the advantages gained by the program have, however, not been explored yet. We investigate this with mathematical models. We find that more programmed divisions can make virus clearance more efficient because CTL division continues to occur independent from antigenic stimulation when virus load drops to low levels. This results in stronger effector activity at low virus loads, and in a higher chance of virus extinction. On the other hand, the more programmed divisions occur, the less efficient the response is at preventing high acute virus loads and thus acute symptoms. The reason is that the programmed divisions are independent from antigenic stimulation, and an increase in virus load does not speed up the rate of CTL expansion. We hypothesize that the 7–10 programmed divisions observed in vivo represent an optimal solution to this trade-off which maximizes the chances to clear, while preventing excessive acute pathology. If the CTLs fail to clear the virus, however, we find that the properties of the programmed proliferation model are very similar to those derived from models which assume continuous antigenic stimulation. We discuss these results in the context of data from murine virus infections and explore implications for virus dynamics in CD4 helper-deficient hosts.

Keywords: mathematical model, programmed CTL proliferation dynamics, CTL homeostasis, effector molecules, CD4 T cell help

Transmitting editor: M. Bevan


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J R Soc InterfaceHome page
D. Wodarz, S. Sierro, and P. Klenerman
Dynamics of killer T cell inflation in viral infections
J R Soc Interface, June 22, 2007; 4(14): 533 - 543.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.