Abstract
Maternal immune tolerance to paternal allo-antigens expressed by the fetus is a precondition of successful pregnancy in viviparous mammals. This occurs despite exposure of the maternal immune system to potentially immunogenic fetal tissue. Local immune evasion mechanisms are thought to prevent maternal immune aggression towards the fetus. Nevertheless, maternal lymphocytes capable of mediating anti-fetal immune aggression are detectable throughout gestation. This review focuses on the role played by regulatory T cells in suppressing alloreactive immune responses, thereby promoting materno-fetal tolerance. The characteristics of naturally occurring regulatory T cells, their function in mouse and human pregnancy and the implications for infertility, premature abortion syndromes, transplantation and autoimmunity are discussed in detail.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Walker LS, Abbas AK. The enemy within: Keeping self-reactive T cells at bay in the periphery. Nat Rev Immunol 2002;2:11–9.
Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat Rev Immunol 2003;3:199–210.
Billington WD. The immunological problem of pregnancy: 50 years with the hope of progress. A tribute to Peter Medawar. J Reprod Immunol 2003;60:1–11.
Thellin O, Coumans B, Zorzi W et al. Tolerance to the foeto-placental ‘graft’: Ten ways to support a child for nine months. Curr Opin Immunol 2000;12:731–7.
Tafuri A, Alferink J, Moller P et al. T cell awareness of paternal alloantigens during pregnancy. Science 1995;270:630–3.
Aluvihare VR, Kallikourdis M, Betz AG. Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 2004;5:266–71.
Munn DH et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 1998;281:1191–3.
Mellor AL et al. Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat Immunol 2001;2:64–8.
Makrigiannakis A et al. Corticotropin-releasing hormone promotes blastocyst implantation and early maternal tolerance. Nat Immunol 2001; 2:1018–24.
Rouas-Freiss N, Goncalves RM, Menier C et al. Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. Proc Natl Acad Sci USA 1997;94:11520–5.
Xu C et al. A critical role for murine complement regulator crry in fetomaternal tolerance. Science 2000;287:498–501.
Piccinni MP et al. Defective production of both leukemia inhibitory factor and type 2 T-helper cytokines by decidual T cells in unexplained recurrent abortions. Nat Med 1998;4:1020–4.
Mattsson R, Mattsson A, Holmdahl R et al. Maintained pregnancy levels of oestrogen afford complete protection from post-partum exacerbation of collagen-induced arthritis. Clin Exp Immunol 1991;85:41–7.
Beagley KW, Gockel CM. Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone. FEMS Immunol Med Microbiol 2003;38:13–22.
Billingham RE, Brent L, Medawar PB. Activity acquired tolerance of foreign cells. Nature 1953;172:603–6.
Sakaguchi S et al. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: Their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev 2001;182:18–32.
Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004;22:531–562.
Shimizu J, Yamazaki S, Takahashi T et al. Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 2002;3:135–42.
Jordan MS et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol 2001;2:301–6.
Apostolou I, Sarukhan A, Klein L et al. Origin of regulatory T cells with known specificity for antigen. Nat Immunol 2002;3:756–63.
Bystry RS, Aluvihare V, Welch KA et al. B cells and professional APCs recruit regulatory T cells via CCL4. Nat Immunol 2001;2:1126–32.
Read S, Powrie F. CD4(+) regulatory T cells. Curr Opin Immunol 2001;13:644–9.
Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003;299:1057–61.
Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003;4:330–6.
Khattri R, Cox T, Yasayko SA et al. An essential role for scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 2003;4:337–42.
Gallimore A, Sakaguchi S. Regulation of tumour immunity by CD25+ T cells. Immunology 2002;107:5–9.
Belkaid Y, Piccirillo CA, Mendez S et al. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 2002;420:502–7.
Bach JF, Francois Bach J. Regulatory T cells under scrutiny. Nat Rev Immunol 2003;3:189–98.
Yamazaki S et al. Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells. J Exp Med 2003;198:235–47
Jonuleit H, Schmitt E, Schuler G et al. Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 2000;192:1213–22.
Pasare C, Medzhitov R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 2003;299:1033–6.
Somerset DA, Zheng Y, Kilby MD et al. Normal human pregnancy is associated with an elevation in the immune suppressive CD25 CD4 regulatory T-cell subset. Immunology 2004;112:38–43.
Sasaki Y et al. Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod 2004;10:347–53.
Heikkinen J, Mottonen M, Alanen A et al. Phenotypic characterization of regulatory T cells in the human decidua. Clin Exp Immunol 2004;136, 373–8.
Fallarino F et al. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 2003;4:1206–12.
Maloy KJ et al. CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med 2003;197:111–9.
Viglietta V, Baecher-Allan C, Weiner HL et al. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 2004;199:971–9.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Eurekah.com and Springer Science+Business Media
About this chapter
Cite this chapter
Aluvihare, V.R., Betz, A.G. (2006). The Role of Regulatory T Cells in Materno-Fetal Tolerance. In: Mor, G. (eds) Immunology of Pregnancy. Medical Intelligence Unit. Springer, New York, NY. https://doi.org/10.1007/0-387-34944-8_16
Download citation
DOI: https://doi.org/10.1007/0-387-34944-8_16
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-30612-4
Online ISBN: 978-0-387-34944-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)