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Title: Phenotypic and functional characterisation of myeloid and plasmacytoid dendritic cells
Author: Singh, Rena
ISNI:       0000 0001 3415 8242
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2006
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Cord blood transplantation (CBT) is an alternative to bone marrow transplantation (BMT) and is associated with a reduced severity of graft versus host disease (GvHD). Recipient and donor dendritic cells (DCs) are involved in the development of GvHD, and two main subsets, myeloid DCs (MDCs) and plasmacytoid DCs (PDCs), with different immunological functions, have been identified in adult peripheral blood (APB). In this thesis, the presence, phenotype and functional characteristics of these two DC subsets were investigated in CB. Absolute cell counts, the expression of a number of markers and the endocytic capacities were studied on highly purified MDCs and PDCs by flow cytometry. The cytokine profile of stimulated DC subsets was determined using a multiple cytokine detection system. The allostimulatory capacity was studied in vitro and the cytokine production of the cultures was also assessed. The results showed the presence of MDCs and PDCs in CB, with PDCs as the predominant population. Surface marker expression differed between CB DC subsets, and levels of expression were generally lower compared to APB. Stimulated CB MDCs and PDCs secreted Thl and Th2 cytokines, respectively. CB MDCs had a higher endocytic capacity than PDCs, as shown for APB. The allostimulatory capacity of CB MDCs was higher than CB and APB PDCs, but lower than APB MDCs. Comparisons of fresh and frozen cells revealed a reduced allostimulatory capacity of frozen CB DC subsets, not apparent in APB. There was preferential secretion of Th2 cytokines following allogeneic stimulation with CB MDCs and PDCs. The results showed different phenotypic and functional characteristics of CB MDCs compared to PDCs. The studies confirmed the immature status of CB DCs and their capacity to mount adult level responses when appropriately stimulated. Therefore, these in vitro studies may help to explain the reduced incidence and severity of GvHD following CBT.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available