Potentiating maternal immune tolerance in pregnancy: A new challenging role for regulatory T cells

J. Alijotas-Reig, E. Llurba, J. M. Gris

Research output: Contribution to journalArticleResearchpeer-review

101 Citations (Scopus)


The maternal immune system needs to adapt to tolerate the semi-allogeneic conceptus. Since maternal allo-reactive lymphocytes are not fully depleted, other local/systemic mechanisms play a key role in altering the immune response. The Th1/Th2 cytokine balance is not essential for a pregnancy to be normal. The immune cells, CD4+CD25+Foxp3+, also known as regulatory T cells (Tregs), step in to regulate the allo-reactive Th1 cells. In this review we discuss the role of Tregs in foeto-maternal immune tolerance and in recurrent miscarriage as well as their potential use as a new target for infertility treatment. Animal and human experiments showed Treg cell number and/or function to be diminished in miscarriages. Murine miscarriage can be prevented by transferring Tregs from normal pregnant mice. Tregs at the maternal-fetal interface prevented fetal allo-rejection by creating a "tolerant" microenvironment characterised by the expression of IL-10, TGF-β and haem oxygenase isoform 1 (HO-1) rather than by lowering Th1 cytokines. Tregs increase placental HO-1. In turn, HO-1 may lead to up-regulation of TGF-β, IL-10 and CTLA-4. In vivo experiments showed Tregs sensitisation from paternal antigens to be essential for maternal-fetal tolerance. Tregs increase throughout pregnancy and diminish in late puerperium. Recent data also support the capacity of Tregs to block maternal effector T cells, thereby reducing the maternal-fetal pathological responses to paternal antigens. These findings also permit us to consider new strategies for improving pregnancy outcomes, i.e., anti-TNF blockers and granulocyte-colony stimulating factors as well as novel approaches to therapeutically exploiting Treg + cell memory. © 2014 Elsevier Ltd.
Original languageEnglish
Pages (from-to)241-248
Issue number4
Publication statusPublished - 1 Jan 2014


  • Cytokines
  • Maternal-fetal tolerance
  • Miscarriages
  • NK cells/KIR
  • Regulatory-T lymphocytes
  • Treatment


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