Regulatory T cells induce a privileged tolerant microenvironment at the fetal‐maternal interface

The mechanisms underlying immune tolerance during pregnancy are poorly understood. In this regard, Treg seem to play an important role in mediating maternal tolerance to the fetus. We proposed a crucial role of T regulatory cells (Treg) in avoiding immunological rejection of the fetus after observin...

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Published in:	European Journal of Immunology Vol. 36; no. 1; pp. 82 - 94
Main Authors:	Zenclussen, Ana C., Gerlof, Katrin, Zenclussen, Maria L., Ritschel, Stefanie, Zambon Bertoja, Annarosa, Fest, Stefan, Hontsu, Shigeto, Ueha, Satoshi, Matsushima, Kouji, Leber, Joachim, Volk, Hans‐Dieter
Format:	Journal Article
Language:	English
Published:	Weinheim WILEY‐VCH Verlag 01-01-2006
Subjects:	Adoptive Transfer Animals CD4 Antigens - immunology CD4 Antigens - metabolism Cytokines - biosynthesis Cytokines - immunology Decidua - immunology Female Fetus - immunology Flow Cytometry Fluorescent Antibody Technique Forkhead box P3 Forkhead Transcription Factors - immunology Forkhead Transcription Factors - metabolism Heme oxygenase‐1 Immune Tolerance Mice Neuropilin-1 - immunology Neuropilin-1 - metabolism Neuropilin‐1 Pregnancy Pregnancy, Animal - immunology Receptors, Interleukin-2 - immunology Receptors, Interleukin-2 - metabolism Regulatory T cells Reproductive immunology Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis T-Lymphocytes, Regulatory - immunology
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Summary:	The mechanisms underlying immune tolerance during pregnancy are poorly understood. In this regard, Treg seem to play an important role in mediating maternal tolerance to the fetus. We proposed a crucial role of T regulatory cells (Treg) in avoiding immunological rejection of the fetus after observing diminished number and function of Treg in abortion‐prone mice. We further confirmed the protective role of Treg during pregnancy by transferring pregnancy‐induced Treg into abortion‐prone mice, which prevented rejection. Here, we analyzed the mechanisms involved in Treg‐mediated protection. As expected, Treg therapy prevented abortion, while expanding the peripheral and thymic Treg population. Surprisingly, the decidual levels of the Th1 cytokines IFN‐γ and TNF‐α were not diminished after therapy. Interestingly, the mRNA levels of leukemia inhibitory factor, TGF‐β and heme oxygenase‐1 at the fetal‐maternal interface were dramatically up‐regulated after Treg transfer, while the levels of indolamine 2,3‐dioxygenase remained unchanged. Our data suggest that Treg treatment can not prevent T cell infiltration or high Th1 levels but is able to create a privileged tolerant microenvironment at the fetal‐maternal interface, further shedding light onto the molecular mechanisms involved in pregnancy tolerance.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-2980 1521-4141 1365-2567
DOI:	10.1002/eji.200535428