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This dissertation, Functional Comparison of Cord and Adult Blood-derived Dendritic Cells by On-hang, Wong, 黃安恆, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Functional Comparison of Cord and Adult Blood- Derived Dendritic Cells submitted by Wong On Hang for the Degree of Master of Philosophy at the University of Hong Kong in August 2004 Neonates are considered immunodeficient because they have an increased susceptibility to infectious agents and poor immune responses are commonly observed. However, recent evidence suggests that fully mature adaptive immune responses can be generated in neonatal mice and humans. Neonatal immunity shows considerable plasticity and may have evolved to achieve low esponsiveness under non-threatening conditions and to mount mature protective responses in dangerous or threatening situations. This unique property of the neonatal immune response is thought to be important in the early development of the organism when the immune cells must establish a tolerant state to the large number of environmental and self antigens encountered in the early postnatal life. Since dendritic cell (DC) is the professional antigen presenting cell which plays a critical role in initiating immunity as well as inducing tolerance to self-antigens, neonatal DC is likely a key player in shaping the neonatal immune response. Normal turnover of peripheral tissues yields apoptotic cells while pathogens or infections cause tissue injuries and necrosis. The interaction of these dying cells with DC may provide immunological instructions leading to either immune tolerance or activation. In this study, we hypothesize that neonatal and adult DC may differ in its interaction with apoptotic and necrotic cells thereby accounting for the observed difference in the immune responses between the neonates and the adults. To test the hypothesis, we compare the interaction of cord blood and adult blood derived DCs with dying Epstein-Barr virus-transformed lymphoblastoid cells (LCLs) under the same experimental conditions and measure the outcome of the interaction in terms of phagocytic function, phenotypic changes, cytokine production and T cell stimulatory capacity of the cord and adult DCs. Cord DCs can upregulate activation markers, produce IL-10 and TNF-α, and exhibit T cell stimulation in response to lipopolysaccharide (LPS). While cord DCs phagocytose apoptotic and necrotic LCLs, the subsequent responses are different as adult DCs. Interaction with early apoptotic LCLs results in minimal upregulation of activation markers, no cytokine production and no T cell stimulation. Interaction with necrotic LCLs results in slight upregulation of activation markers, no cytokine production and weak T cell stimulation. This contrasts with adult DCs which upregulate activation markers, produce IL-10 and TNF-α, and exhibit T cell stimulation, after phagocytosing necrotic LCLs. In addition, cord DCs appear poor producers of interlukin-12, implying a deviation from Th1 type responses. Taken together, these results may support the notion that neonatal DC shows variation in its response depending on the signal it encounters. In normal cell turnover and even in inflammatory situations (represented by interaction with early apoptotic and necrotic LCLs, respectively), neonatal DC response seems to favour immune tolerance with minimal activation and cytokine production. In dangerous situations such as bacterial sepsis (represented by interaction with LPS) neonatal DC activates

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