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Human Reproduction Update Advance Access originally published online on March 11, 2009
Human Reproduction Update 2009 15(5):517-535; doi:10.1093/humupd/dmp004
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment?

Leigh R. Guerin1, Jelmer R. Prins1,2 and Sarah A. Robertson1,3

1 Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, SA 5005, Australia 2 Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, The Netherlands

3 Correspondence address. Tel: +61-8-8303-4094; Fax: +61-8-8303-4099; E-mail: sarah.robertson{at}adelaide.edu.au

BACKGROUND: Adaptation of the maternal immune response to accommodate the semi-allogeneic fetus is necessary for pregnancy success, and disturbances in maternal tolerance are implicated in infertility and reproductive pathologies. T regulatory (Treg) cells are a recently discovered subset of T-lymphocytes with potent suppressive activity and pivotal roles in curtailing destructive immune responses and preventing autoimmune disease.

METHODS: A systematic review was undertaken of the published literature on Treg cells in the ovary, testes, uterus and gestational tissues in pregnancy, and their link with infertility, miscarriage and pathologies of pregnancy. An overview of current knowledge on the generation, activation and modes of action of Treg cells in controlling immune responses is provided, and strategies for manipulating regulatory T-cells for potential applications in reproductive medicine are discussed.

RESULTS: Studies in mouse models show that Treg cells are essential for maternal tolerance of the conceptus, and that expansion of the Treg cell pool through antigen-specific and antigen non-specific pathways allows their suppressive actions to be exerted in the critical peri-implantation phase of pregnancy. In women, Treg cells accumulate in the decidua and are elevated in maternal blood from early in the first trimester. Inadequate numbers of Treg cells or their functional deficiency are linked with infertility, miscarriage and pre-eclampsia.

CONCLUSIONS: The potency and wide-ranging involvement of Treg cells in immune homeostasis and disease pathology indicates the considerable potential of these cells as therapeutic agents, raising the prospect of their utility in novel treatments for reproductive pathologies.

Key words: pregnancy / infertility / cytokines / regulatory T-cells / tolerance / immune suppression

Received on September 24, 2008; revised December 28, 2008; accepted on January 23, 2009


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