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Regulatory T cells mediate maternal tolerance to the fetus

Nature Immunology volume 5, pages 266–271 (2004)Cite this article

Abstract

Pregnancy constitutes a major challenge to the maternal immune system, as it has to tolerate the persistence of paternal alloantigen. Although localized mechanisms contribute to fetal evasion from immune attack, maternal alloreactive lymphocytes persist. We demonstrate here an alloantigen-independent, systemic expansion of the maternal CD25+ T cell pool during pregnancy and show that this population contains dominant regulatory T cell activity. In addition to their function in suppressing autoimmune responses, maternal regulatory T cells suppressed an aggressive allogeneic response directed against the fetus. Their absence led to a failure of gestation due to immunological rejection of the fetus.

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Figure 1: CD4+CD25+ T cell pools of pregnant and nonpregnant mice.
Figure 2: Kinetics of the expansion of the CD4+CD25+ T cell pool in syngeneic pregnancies.
Figure 3: Suppression of alloreactive proliferation by CD25+ regulatory cells.
Figure 4: Regulatory T cells in the gravid uterus.
Figure 5: Regulatory T cells prevent rejection of the fetal allograft.

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Acknowledgements

We thank R. Bystry for help with the immunohistochemistry; M.S. Neuberger, D.T. Fearon, K.J. Patel and F. Randow for critical reading of the manuscript; M. Bradley (Centre for Applied Medical Statistics, University of Cambridge) for statistical advice; and T. Langford, L. Stuckey, V. Smith, M. Brown and G. Ledger for help with technical animal procedures. All work was done at the Laboratory of Molecular Biology and funded by the Medical Research Council.

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  1. Varuna R Aluvihare and Alexander G Betz: These authors contributed equally to this work.

Authors and Affiliations

  1. Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, United Kingdom

    Varuna R Aluvihare, Marinos Kallikourdis & Alexander G Betz

  2. Department of Medicine, Addenbrooke's NHS Trust, Hills Road, Cambridge, CB2 2YH, United Kingdom

    Varuna R Aluvihare

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  1. Varuna R Aluvihare
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Correspondence to Varuna R Aluvihare or Alexander G Betz.

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Aluvihare, V., Kallikourdis, M. & Betz, A. Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 5, 266–271 (2004). https://doi.org/10.1038/ni1037

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