Fetal-specific CD8+ cytotoxic T cell responses develop during normal human pregnancy and exhibit broad functional capacity.
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.
School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK. d.m.lissauer@bham.ac.uk
David
D
Lissauer
Karen
K
Piper
Oliver
O
Goodyear
Mark D
MD
Kilby
Paul A H
PA
Moss
D056704:Adaptive Immunity / Q000276:immunology; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D053595:Embryonic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000097:blood / Q000276:immunology*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000276:immunology*; D006182:H-Y Antigen / Q000097:blood / Q000276:immunology; D015789:HLA-A2 Antigen / Q000097:blood / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000097:blood / Q000276:immunology; D011247:Pregnancy; D055503:Protein Multimerization / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D006182:H-Y Antigen; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D015778:Minor Histocompatibility Antigens