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

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http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/21836 http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/21836 http://eprints.org/relation/isIndexCodesVersionOf http://etheses.bham.ac.uk/id/document/21836 archive 4031 disk0/00/00/36/13 2012-07-31 10:50:02 2019-01-17 17:03:48 2012-07-31 10:50:01 thesis show 0 Lissauer David Michael Kilby Mark D. Moss Paul A. University of Birmingham The biological and clinical significance of the maternal immune response to fetal antigens unpub QH301 QR180 RG 10col_mede 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their function, which may have therapeutic implications. 2012-12 2012-07 graduation eng author unchecked This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. public 294 University of Birmingham School of Clinical and Experimental Medicine d_ph na 2012-12 graduation