Lissauer, David Michael (2012). The biological and clinical significance of the maternal immune response to fetal antigens. University of Birmingham. Ph.D.
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Lissauer12PhD.pdf
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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: | Thesis (Doctorates > Ph.D.) | |||||||||
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Award Type: | Doctorates > Ph.D. | |||||||||
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College/Faculty: | Colleges (2008 onwards) > College of Medical & Dental Sciences | |||||||||
School or Department: | School of Clinical and Experimental Medicine | |||||||||
Funders: | None/not applicable | |||||||||
Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QR Microbiology > QR180 Immunology R Medicine > RG Gynecology and obstetrics |
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URI: | http://etheses.bham.ac.uk/id/eprint/3613 |
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