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

D Lissauer, K Piper, O Goodyear, MD Kilby… - The Journal of …, 2012 - journals.aai.org
D Lissauer, K Piper, O Goodyear, MD Kilby, PAH Moss
The Journal of Immunology, 2012journals.aai.org
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 …
Abstract
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.
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