The evolutionary adaptation in mammals that allows implantation of their embryos in the mother's womb creates an immunological problem. Although it ensures optimal nourishment and protection of the fetus throughout its early development, intimate contact with the mother's uterine tissue makes the fetus a potential target for her immune system. As half the fetal genes are derived from the father, the developing embryo and placenta must be considered a 'semi-allograft'. Such a mismatched organ transplant would be readily rejected without powerful immune suppression. During pregnancy, however, the semi-allogeneic fetus is protected from assault by the maternal immune system over an extended period of time. The mother's immune system seems to recognize the fetus as 'temporary self'. How this feat is managed is key to understanding immunological tolerance and intervention in treating disease.
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We thank G. Gruetz, M. Kallikourdis and A. Moffett for critical reading of the manuscript, and E. Long and S. Rajagopalan for access to data in the press. Supported by the Wellcome Trust (J.T.) and the Medical Research Council (J.T. and A.G.B.).
The authors declare no competing financial interests.
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Trowsdale, J., Betz, A. Mother's little helpers: mechanisms of maternal-fetal tolerance. Nat Immunol 7, 241–246 (2006). https://doi.org/10.1038/ni1317
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