Fetal-specific CD8+ cytotoxic T cell responses develop during normal human pregnancy and exhibit broad functional capacity

J Immunol. 2012 Jul 15;189(2):1072-80. doi: 10.4049/jimmunol.1200544. Epub 2012 Jun 8.


Tolerance of the semiallogeneic fetus presents a significant challenge to the maternal immune system during human pregnancy. T cells with specificity for fetal epitopes have been detected in women with a history of previous pregnancy, but it has been thought that such fetal-specific cells were generally deleted during pregnancy as a mechanism to maintain maternal tolerance of the fetus. We used MHC-peptide dextramer multimers containing an immunodominant peptide derived from HY to identify fetal-specific T cells in women who were pregnant with a male fetus. Fetal-specific CD8(+) T lymphocytes were observed in half of all pregnancies and often became detectable from the first trimester. The fetal-specific immune response increased during pregnancy and persisted in the postnatal period. Fetal-specific cells demonstrated an effector memory phenotype and were broadly functional. They retained their ability to proliferate, secrete IFN-γ, and lyse target cells following recognition of naturally processed peptide on male cells. These data show that the development of a fetal-specific adaptive cellular immune response is a normal consequence of human pregnancy and that unlike reports from some murine models, fetal-specific T cells are not deleted during human pregnancy. This has broad implications for study of the natural physiology of pregnancy and for the understanding of pregnancy-related complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology
  • Clone Cells
  • Cytotoxicity Tests, Immunologic / methods
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / immunology*
  • Embryonic Stem Cells / metabolism*
  • Epitopes, T-Lymphocyte / blood
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Fetus / cytology
  • Fetus / immunology*
  • H-Y Antigen / blood
  • H-Y Antigen / immunology
  • HLA-A2 Antigen / blood
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunophenotyping
  • Male
  • Minor Histocompatibility Antigens / blood
  • Minor Histocompatibility Antigens / immunology
  • Pregnancy
  • Protein Multimerization / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism


  • Epitopes, T-Lymphocyte
  • H-Y Antigen
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Minor Histocompatibility Antigens