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Title: Changes in cord blood dendritic cells as biomarkers of fetal exposure to stressor stimuli
Author: Oliver, Reeba
ISNI:       0000 0005 0734 572X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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DCs are central to fetal defences and it was postulated that phenotypic changes on CBDCs in response to infectious/stressor stimuli could identify compromised fetuses. Investigations were performed on whole blood using monoclonal antibody labelling and flow cytometry. Functional studies included endocytosis of Dextran particles and MLR. Both plasmacytoid (HLA-DR+CD11c−) and myeloid (HLA-DR+CD11c+) DCs were identified in CB. Additionally CB contained a DC subset with a HLA-DR+CD11c−CD45^intermediate(inm) phenotype. This population expressed lower levels of CD45 and HLA-DR and did not express plasmacytoid (CD123, BDCA2, and CD45RA) or myeloid (CD33 and CD13) markers. All subsets exhibited endocytosis and unlabelled CBDCs exhibited lymphocytic stimulatory capacity. Both myeloid and plasmacytoid CBDC subsets showed no change with gestation. The CD11c− CD45^inm subset decreased with increasing gestation representing 31.33% of total DCs in preterm, 21.26% in term CB and 1.54% in adult PB. CD11c−CD45inm DC numbers expressing CD40, CD86 and production of IL-12 increased significantly with stressors. The myeloid and the plasmacytoid subsets showed no upregulation of CD40 and CD86 with stressors. The myeloid subset decreased while the plasmacytoid subset increased IL-12 production with stressors. Neutrophilic activation markers of CD11b and CD16 showed significant correlation with the stressed CB samples which exhibited proinflammatory DC responses, thus validating the clinical classification. These data indicate that CB contains plasmacytoid and myeloid DC populations as seen in adult PB. Additionally this study has identified a hitherto unreported CBDC subset with an immature phenotype, exhibiting endocytosis and phenotypically distinct from plasmacytoid DCs. Of the three subsets, only the CD11c−CD45^inm subset showed a costimulatory response to stressors suggesting this subset to be the most kinetic; changing with advancing gestation as well as exposure to stressors. Thus investigating phenotypic changes on CBDC subsets, especially on the CD11c−CD45^inm subset, could serve to identify fetuses exposed to stressor stimuli and at risk of adverse sequelae.
Supervisor: Knight, Stella ; Lamont, Ronnie ; Stagg, Andrew Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral