Tumor emergence is sensed by self-specific CD44(hi) memory Tregs that create a dominant tolerogenic environment for tumors in mice

Darrasse-Jeze, Guillaume, Bergot, Anne-Sophie, Durgeau, Aurelie, Billiard, Fabienne, Salomon, Benoit L., Cohen, Jose L., Bellier, Bertrand, Podsypanina, Katrina and Klatzmann, David (2009) Tumor emergence is sensed by self-specific CD44(hi) memory Tregs that create a dominant tolerogenic environment for tumors in mice. Journal of Clinical Investigation, 119 9: 2648-2662. doi:10.1172/JCI36628


Author Darrasse-Jeze, Guillaume
Bergot, Anne-Sophie
Durgeau, Aurelie
Billiard, Fabienne
Salomon, Benoit L.
Cohen, Jose L.
Bellier, Bertrand
Podsypanina, Katrina
Klatzmann, David
Title Tumor emergence is sensed by self-specific CD44(hi) memory Tregs that create a dominant tolerogenic environment for tumors in mice
Formatted title
Tumor emergence is sensed by self-specific CD44hi memory Tregs that create a dominant tolerogenic environment for tumors in mice
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
1558-8238
Publication date 2009-09-01
Sub-type Article (original research)
DOI 10.1172/JCI36628
Open Access Status DOI
Volume 119
Issue 9
Start page 2648
End page 2662
Total pages 15
Place of publication Ann Arbor, MI, United States
Publisher American Society for Clinical Investigation
Language eng
Abstract Early responses of Tregs and effector T cells (Teffs) to their first encounter with tumor cells have been poorly characterized. Here we have shown, in both implanted and in situ–induced mouse tumor models, that the appearance of tumor cells is immediately sensed by CD44hi memory Tregs that are specific for self antigens. The rapid response of these Tregs preceded and prevented activation of naive antitumor Teffs. The relative speed of the Treg versus the Teff response within the first 2–4 days determined the outcome of the antitumor immune response: tolerance or rejection. If antitumor memory Teffs were present at the time of tumor emergence, both Tregs and Teffs were recruited and activated with memory kinetics; however, the Tregs were unable to control the Teffs, which eradicated the tumor cells. This balance between effector and regulatory responses did not depend on the number of Tregs and Teffs, but rather on their memory status. Thus, in the natural setting, dominant tolerogenic immunosurveillance by self-specific memory Tregs protects tumors, just as it protects normal tissues. More generally, our results reveal that the timing of Treg and Teff engagement, determined by their memory status, is an important mode of regulation of immune responses.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 57 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 67 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 21 Nov 2011, 10:41:35 EST by System User on behalf of UQ Diamantina Institute