Modification of dendritic cell phenotype and function : consequences for allergic asthma

The initial work aimed to characterise monocyte-derived dendritic cells (Mo-DCs) from normal and asthmatic subjects to identify inherited differences with possible relevance for allergic asthma. It was found that Mo-DCs from asthmatic subjects expressed significantly lower level of CD23 at their surface and produced more IL-6 than Mo-DCs from normal subjects.A primary screen was then developed to address the hypothesis. The primary screen aimed to identify individual agents found at elevated levels in the asthmatic lung, referred to as allergic mediators, that significantly change the phenotype or function of Mo-DCs. Further in-depth investigation of their effects on Mo-DCs and possible relevance in allergic asthma would then be conducted. The effects of allergic mediators on Mo-DCs from both normal and asthmatic subjects were studied. The experimental approach taken showed that the Mo-DC phenotype and function was significantly changed in response to TNF-α (the positive control), IFN-γ, IL-3, IL-5 and IgE, but not in response to MMIP-1α, histamine, PGD2 and IL-13. Four areas of particular interest were identified. 1) Phenotypically mature IFN-γ treated Mo-DCs failed to significantly enhance T cell proliferation. 2) CD23 disappeared from the surface of Mo-DCs in response to TNF-α, IFN-γ and IgE. 3) IL-3 and IL-5 frequently induced a mature Mo-DC phenotype. 4) Mo-DCs from normal and asthmatic subjects responded differently to allergic mediators.The work presented in this thesis supports a role for DCs in allergic asthma. Evidence also suggested that DCs from asthmatic subjects are more prone to initiate or perpetuate the chronic allergic inflammation seen in asthmatic airways.