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International Immunology Advance Access originally published online on July 14, 2008
International Immunology 2008 20(9):1147-1154; doi:10.1093/intimm/dxn072
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Characterization of a lymphocyte subset displaying a unique regulatory activity in human decidua

Hagai Amsalem1,2, Anat Gaiger1, Sa'ar Mizrahi3, Simcha Yagel2 and Jacob Rachmilewitz1

1 Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel
2 Department of Obstetrics and Gynecology, Hadassah University Hospital-Mount Scopus, Jerusalem, Israel
3 Lautenberg Center for General and Tumor Immunology, the Hebrew University-Hadassah Medical School, Jerusalem, Israel

Correspondence to: H. Amsalem; E-mail: hagai223{at}gmail.com

One of the most intriguing mechanisms of early pregnancy is the maternal immune tolerance toward her semi-allogeneic fetus, specifically in face of the accumulation of lymphocytes to high numbers at implantation sites. Here, we propose that a regulatory decidual lymphocyte (dL) population prevent the activation of reactive T cells and by that may maintain immune tolerance in the decidua. dLs were isolated from first trimester decidua and were then co-cultured with PBMC that were stimulated with anti-CD3 mAbs. Cytokine secretion to the media as well as the proliferative response were tested. The data demonstrate that dLs inhibit the production of IFN-{gamma}, tumor necrosis factor-{alpha} (TNF-{alpha}) and IL-5 but not CD25 expression, IL-2 production or proliferation in the responder PBMC. Suppression is mediated by a cell contact-dependent mechanism, was not restricted by the MHC and was not reversed by the addition of exogenous IL-2 although the inhibitory sub-population was identified as CD3+CD4+CD25+Foxp3+ natural regulatory T cells (Treg). Interestingly, suppression can also be overcome by the addition the endotoxin LPS, suggesting a mechanism for preterm labor triggered by chorioamnionitis. While these characteristics are in contrast to known peripheral CD4+CD25+ Treg activity, we identified these cells as the cellular subset responsible for the regulatory activity, suggesting that in decidua a functionally unique regulatory lymphocyte subset exist. These findings suggest the existence of a dynamic regulatory system in human decidua that is highly responsive to environmental factors.

Keywords: decidua, lipopolysaccharide, suppression, T cells, tolerance

Transmitting editor: M. Feldmann

Received 1 August 2007, accepted 5 June 2008.


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