PMID- 24581729
OWN - NLM
STAT- MEDLINE
DCOM- 20141121
LR  - 20140321
IS  - 1532-3102 (Electronic)
IS  - 0143-4004 (Linking)
VI  - 35
IP  - 4
DP  - 2014 Apr
TI  - Potentiating maternal immune tolerance in pregnancy: a new challenging role for 
      regulatory T cells.
PG  - 241-8
LID - S0143-4004(14)00059-9 [pii]
LID - 10.1016/j.placenta.2014.02.004 [doi]
AB  - 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-beta 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-beta, 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.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Alijotas-Reig, J
AU  - Alijotas-Reig J
AD  - Systemic Autoimmune Disease Unit, Department of Internal Medicine I, Vall 
      d'Hebron University Hospital, Passeig Vall d'Hebron 119-129, 08035 Barcelona, 
      Spain; Department of Medicine, Faculty of Medicine, Universitat Autonoma, 
      Barcelona, Spain. Electronic address: 16297jar@comb.es.
FAU - Llurba, E
AU  - Llurba E
AD  - High Obstetric Risk Unit, Obstetric Department, Vall d'Hebron University 
      Hospital, Universitat Autonoma, Barcelona, Spain.
FAU - Gris, J Ma
AU  - Gris JM
AD  - Reproductive Medicine Unit, Obstetric Department, Vall d'Hebron University 
      Hospital, Universitat Autonoma, Barcelona, Spain.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20140214
PL  - Netherlands
TA  - Placenta
JT  - Placenta
JID - 8006349
SB  - IM
MH  - Abortion, Spontaneous/immunology
MH  - Animals
MH  - Female
MH  - Humans
MH  - *Immune Tolerance
MH  - Infertility, Female/immunology
MH  - Pregnancy/*immunology
MH  - T-Lymphocytes, Regulatory/*physiology
OTO - NOTNLM
OT  - Cytokines
OT  - Maternal-fetal tolerance
OT  - Miscarriages
OT  - NK cells/KIR
OT  - Regulatory-T lymphocytes
OT  - Treatment
EDAT- 2014/03/04 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/03/04 06:00
PHST- 2013/10/10 00:00 [received]
PHST- 2014/01/30 00:00 [revised]
PHST- 2014/02/04 00:00 [accepted]
PHST- 2014/03/04 06:00 [entrez]
PHST- 2014/03/04 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S0143-4004(14)00059-9 [pii]
AID - 10.1016/j.placenta.2014.02.004 [doi]
PST - ppublish
SO  - Placenta. 2014 Apr;35(4):241-8. doi: 10.1016/j.placenta.2014.02.004. Epub 2014 
      Feb 14.