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Title: The use of human monocyte-derived dendritic cells as a tool for vaccine studies
Author: Okoye, Isobel Susan
ISNI:       0000 0001 3455 9708
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2008
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This study describes the use of human MoDDCs to study memory T cell differentiation from naïve cells, using two in vitro priming systems. Naïve peripheral blood T cells were stimulated with Staphylococcal Enterotoxin B (SEB) or Melanoma Antigen Recognised by T cells-1 (MART-1)-pulsed MoDDCs. Cells were cultured for up to four weeks and phenotypic and functional analyses carried out to determine the pathway of memory T cell differentiation. SEB and MART-1 in vitro systems differed on the basis of CCR7 expression. CCR7+ SEB-responding CD4+ and CD8+ T cells were prominent at early stages of the culture in contrast to MART-1 pentamer-positive CD8+ T cells which expressed this marker at later time-points post-in vitro stimulation. CD4 and CD8 T cells responding to SEB-stimulation and MART-1 pentamer-positive CD8+ T cells re-expressed CD45RA and IL-7R at late time-points (between days 21 and 28). This was suggestive of memory T cell differentiation based on findings from published studies. T cells however suggested differences between in vivo and in vitro differentiation of T cells. High expression of the aforementioned markers implied the occurrence of early to intermediate-stage cells. These results suggest that in vitro stimulated CD4+ and CD8+ T cells undergo a progressive pathway of differentiation, governed by stimulation strength. The predominance of early-stage central memory-like T cells in the two systems indicates stimulation strengths not sufficient enough to promote effector T cell differentiation in vitro. This was confirmed by low levels of perforin expression and lack of CD45RA+CD27-terminally differentiated CD8+ T cells. Our findings support a progressive differentiation model from central to effector cells during primary in vitro responses. They also suggest the need for the provision of additional factors which may promote effector T cell differentiation in vitro.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available