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 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.
Zenclussen
Ana C
AC
Institute of Medical Immunology, Charité, Medical University Berlin, Berlin, Germany. ana.zenclussen@charite.de
Gerlof
Katrin
K
Zenclussen
Maria L
ML
Ritschel
Stefanie
S
Zambon Bertoja
Annarosa
A
Fest
Stefan
S
Hontsu
Shigeto
S
Ueha
Satoshi
S
Matsushima
Kouji
K
Leber
Joachim
J
Volk
Hans-Dieter
HD
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*
D015704:CD4 Antigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D039942:Neuropilin-1