Self-specific memory regulatory T cells protect embryos at implantation in mice

Chen, Ting, Darrasse-Jeze, Guillaume, Bergot, Anne-Sophie, Courau, Tristan, Churlaud, Guillaume, Valdivia, Karina, Strominger, Jack L., Ruocco, Maria Grazia, Chaouat, Gerard and Klatzmann, David (2013) Self-specific memory regulatory T cells protect embryos at implantation in mice. The Journal of Immunology, 191 5: 2273-2281. doi:10.4049/jimmunol.1202413

Author Chen, Ting
Darrasse-Jeze, Guillaume
Bergot, Anne-Sophie
Courau, Tristan
Churlaud, Guillaume
Valdivia, Karina
Strominger, Jack L.
Ruocco, Maria Grazia
Chaouat, Gerard
Klatzmann, David
Title Self-specific memory regulatory T cells protect embryos at implantation in mice
Journal name The Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2013-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.4049/jimmunol.1202413
Open Access Status DOI
Volume 191
Issue 5
Start page 2273
End page 2281
Total pages 9
Place of publication Bethesda MD, U.S.A.
Publisher American Association of Immunologists
Language eng
Formatted abstract
 Regulatory T cells (Tregs) play crucial roles in both fetal and tumor development. We recently showed that immunosurveillance by pre-existing CD44highCD62Llow activated/memory Tregs (amTregs) specific for self-Ags protects emergent tumor cells in mice. This Treg response of a memory type is more rapid than and dominates the antitumor response of tumor-specific effector T cells. In this study, we report striking similarities between the early Treg responses to embryo and tumor implantation. Tregs are rapidly recruited to uterus-draining lymph nodes and activated in the first days after embryo implantation in both syngeneic and allogeneic matings; express the markers of the amTreg subset; and are at least in part self-Ag specific, as seen in tumor emergence. Unlike in the tumor emergence setting, however, for which preimmunization against tumor Ags is sufficient for complete tumor eradication even in the presence of Tregs, Treg depletion is additionally required for high frequencies of fetus loss after preimmunization against paternal tissue Ags. Thus, amTregs play a major role in protecting embryos in both naive and preimmune settings. This role and the ensuing therapeutic potential are further highlighted by showing that Treg stimulation, directly by lowdose IL-2 or indirectly by Fms-related tyrosine kinase 3 ligand, led to normal pregnancy rates in a spontaneous abortion-prone model.
Keyword Ligand
Protein Kinase
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID LT00291/2008
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 41 times in Thomson Reuters Web of Science Article | Citations
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Created: Sat, 01 Mar 2014, 22:54:36 EST by Dr Anne-sophie Bergot on behalf of UQ Diamantina Institute