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Title: The characterisation of human umbilical cord blood regulatory T cell subsets
Author: Hirani, S.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2012
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Umbilical cord blood (CB) is recognised to be a valuable alternative to bone marrow (BM) as a source of hematopoietic stem cells (HSC). The occurrence of Graft vs. Host Disease (GvHD) after CB transplantation has been reported to be less severe in comparison to BM transplants. In addition to the naive state of immune cells, the action of immuno-suppressive cells such as regulatory T cells (Treg) may contribute to the positive aspects observed in CB transplants. This study investigated the phenotypic and functional characteristics of CB Treg and their potential for expansion in culture. In addition, the allogeneic response of CB and AB CD4+ cells was compared. Two main subsets of Treg have been described: resting (CD45RA+FOXP3low) and activated (CD45RA-FOXP3high). Results presented here showed that CB contained mostly resting Treg whereas AB contained mostly activated Treg. In addition, freshly isolated CB Treg were less capable of inhibiting the proliferation of responses in comparison to AB Treg. CB Treg acquired an activated Treg phenotype and potent suppressive activity after expansion, and expanded CD25+ cultures maintained Treg characteristics for longer in comparison to CD25+ cells expanded from AB. Importantly, unlike AB Treg, expanded CB Treg suppressed the proliferation of autologous and allogeneic responders equally. Finally, ‘putative Treg’ were induced from CB CD25- cells following allogeneic stimulation, the putative Treg were CD4+FOXP3+CD25+CTLA-4+ and were capable of suppressing the proliferation and cytokine responses to primary and subsequent allogeneic challenges. In conclusion, Treg subsets from CB display different phenotypic and functional properties to AB Treg. These properties of CB Treg may clarify the cellular interactions in clinical settings in which CB is currently used and highlight potential future uses.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available