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Title: In vitro characterisation of the Leishmania-dendritic cell interaction
Author: Bennett, Clare Louise
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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In initial experiments, lines of transgenic parasites were generated in which the MHC II-dependent T cell epitope Moth Cytochrome C (MCC) was expressed within a number of different fusion proteins, to provide a model in which the fate of parasite-derived antigens could be followed in infected DC. MHC II-MCC complex formation in CD and MΦ complex-specific T cell line. Although the fusion proteins were clearly demonstrated to be secreted at high levels, no cell surface staining could be detected with D4 and neither infected DC nor infected MΦ could stimulate T cell proliferation. Leishmania-infected DC were however, shown to efficiently process and present exogenous antigen to T cells in vitro. Alternative strategies were therefore developed to probe the DC:Leishmania interaction in more detail. Investigation into the effect of uptake of EGFP-expressing L. mexicana parasites by different DC cultures in vitro demonstrated that, in the absence of exogenous factors, uptake of L. mexicana amastigotes did not cause activation of DC. Uptake of L. mexicana promastigotes resulted in activation of a small proportion of DC indicating that promastigotes do encode an activation signal, but that this is not sufficient to activate the entire DC population. However, neither L. major promastigotes nor L. mexicana promastigote mutants lacking surface lipophosphoglycan (LPG) activated DC in vitro. Therefore these data suggest that L. mexicana promastigotes encode an activation signal, but that this is not sufficient to stimulate all DC. As the promastigotes which did not activate DC either lacked, or expressed a modified version of, LPG, we propose that LPG is a L. mexicana pathogen-associated molecular pattern (PAMP). The work presented in this thesis demonstrates that infected DC are capable of initiating that anti-Leishmania response in vivo, as they efficiently present antigen to T cells. However, infection per se is not sufficient to activate all DC. These data therefore suggest that during the initiation of an anti-Leishmania T cell response DC are likely to be activated by factors produced in response to injection of parasites by the insect vector, such as pro-inflammatory cytokines.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available