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# The biological and clinical significance of the maternal immune response to fetal antigens

Lissauer, David Michael (2012)
Ph.D. thesis, University of Birmingham.

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## Abstract

Tolerance of the semi-allogeneic fetus presents a significant challenge to the maternal immune system. The effect of pregnancy on maternal cellular immunity was established by assessing maternal effector and regulatory T-cell subsets during human pregnancy. This demonstrated that an increase in maternal peripheral regulatory T-cells or a shift from a Th1 to Th2 phenotype was not a requirement for normal pregnancy. We also determined the profound impact of maternal Cytomegalovirus seropositivity on maternal T- cell dynamics. T-cells with specificity for fetal epitopes have been detected in women with a history of pregnancy but it has been thought that such fetal specific cells were deleted during pregnancy. We identified, using MHC-peptide multimers, fetal-specific CD8 T-cells in half of all pregnancies. The fetal-specific response increased during pregnancy and persisted in the post natal period. Fetal-specific cells demonstrated an effector memory phenotype and retained functional potential. These data show that the development of a fetal-specific adaptive cellular immune response is a normal consequence of human pregnancy. Women with recurrent miscarriage were found to have abnormal T-cell function, with increased IFN$$\gamma$$ and Il-17 production. Fetal specific T-cells were also detected in this cohort and progesterone attenuated their function, which may have therapeutic implications.

Type of Work: Ph.D. thesis. Kilby, Mark D and Moss, Paul (Professor) Colleges (2008 onwards) > College of Medical & Dental Sciences School of Clinical and Experimental Medicine QH301 BiologyQR180 ImmunologyRG Gynecology and obstetrics University of Birmingham 3613
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