title: Regulatory T cells induce a privileged tolerant microenvironment at the fetal-maternal interface.
abstract: 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-gamma and TNF-alpha were not diminished after therapy. Interestingly, the mRNA levels of leukemia inhibitory factor, TGF-beta 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.
authors.affiliation: Institute of Medical Immunology, Charité, Medical University Berlin, Berlin, Germany. ana.zenclussen@charite.de
authors.forename: Ana C
authors.initials: AC
authors.lastname: Zenclussen
authors.forename: Katrin
authors.initials: K
authors.lastname: Gerlof
authors.forename: Maria L
authors.initials: ML
authors.lastname: Zenclussen
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ritschel
authors.forename: Annarosa
authors.initials: A
authors.lastname: Zambon Bertoja
authors.forename: Stefan
authors.initials: S
authors.lastname: Fest
authors.forename: Shigeto
authors.initials: S
authors.lastname: Hontsu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueha
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Joachim
authors.initials: J
authors.lastname: Leber
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003656:Decidua / Q000276:immunology*; D005260:Female; D005333:Fetus / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance; D051379:Mice; D039942:Neuropilin-1 / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D039942:Neuropilin-1