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

Eur J Immunol. 2006 Jan;36(1):82-94. doi: 10.1002/eji.200535428.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Decidua / immunology*
  • Female
  • Fetus / immunology*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Immune Tolerance*
  • Mice
  • Neuropilin-1 / immunology
  • Neuropilin-1 / metabolism
  • Pregnancy
  • Pregnancy, Animal / immunology*
  • RNA, Messenger / analysis
  • Receptors, Interleukin-2 / immunology
  • Receptors, Interleukin-2 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • CD4 Antigens
  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • RNA, Messenger
  • Receptors, Interleukin-2
  • Neuropilin-1