Regulatory T cells mediate maternal tolerance to the fetus

Nat Immunol. 2004 Mar;5(3):266-71. doi: 10.1038/ni1037. Epub 2004 Feb 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / classification
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • Female
  • Fetus / anatomy & histology
  • Fetus / immunology*
  • Forkhead Transcription Factors
  • Immune Tolerance*
  • Isoantigens / immunology
  • Lymphocyte Activation
  • Lymphocyte Culture Test, Mixed
  • Lymphocyte Depletion
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Pregnancy / immunology*
  • Pregnancy Outcome
  • Receptors, Interleukin-2 / analysis
  • Uterus / cytology
  • Uterus / immunology


  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Isoantigens
  • Receptors, Interleukin-2