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Tesi di dottorato in medicina >
Please use this identifier to cite or link to this item:
http://hdl.handle.net/2108/586
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Full metadata record
| DC Field | Value | Language |
|---|
| contributor.advisor | Angelini, Federica | - |
| contributor.author | Pacciani, Valentina | - |
| date.accessioned | 2008-08-28T09:53:44Z | - |
| date.available | 2008-08-28T09:53:44Z | - |
| date.issued | 2008-08-28T09:53:44Z | - |
| identifier.uri | http://hdl.handle.net/2108/586 | - |
| description | 19. ciclo | en |
| description.abstract | Several lines of evidence indicate that a defect in immunoregulatory mechanisms is involved in the pathogenesis of allergic asthma.
The aim of this study is to determine whether IL-10-treated dendritic cells (DC) are able to modulate allergen-specific T cell responses in children affected by allergic asthma.
41 children (4-14 years) allergic to House Dust Mite (HDM), and 10 healthy age-matched children were recruited. DC were differentiated from peripheral blood CD14+ precursors and cultured with GM-CSF and IL-4 for 5 days. Der p2 (a major HDM allergen) was added alone or in combination with IL-10 for 48 hours to obtain Dp2-DC and IL10 Dp2-DC, respectively. Alternatively, DC were differentiated in the presence of IL-10 and pulsed with Der p2 during the 2 last days of culture (Dp2-DC10).
The ability of the resulting DC to stimulate allergen-specific autologous T cells and to promote allergen-specific T cell anergy was analyzed.
Dp2-DC induced allergen-specific T cell proliferation in 32 out of 41 patients but not in healthy controls. In 25 out of 26 allergic patients IL10 Dp2-DC and Dp2 DC10 induced a significantly lower allergen-specific T cell proliferation. The analysis of DC phenotype showed that IL-10 treatment significantly downregulated CD86 expression on Dp2-DC. However, no correlation between the reduction of CD86 expression and of T cell proliferation was observed. Dp2-DC stimulation induced a Th2 cytokine profile characterized by an increase of IL-5, IL-13 and IL-4 production and IL-5/IFN-gamma ratio. In the same patients, the co-culture with both IL-10 Dp2-DC and Dp2-DC10 caused a marked reduction of IL-5 production and of IL-13, with a parallel decrease of IL-5/IFN-gamma ratio. Moreover, in 8 children we observed an increase in IL-10 production.
T cell lines generated with Dp2-DC10, compared to those generate with Dp2-DC, were hyporesponsive to reactivation with Der p2 in 4 out of 5 patients tested, both in terms of proliferation and cytokine production: IL-5, IL-13, and IL-5/IFN-gamma ratio.
Our data show that IL-10 reduced the stimulatory capacity of DC through a mechanism independent from the downregulation of costimulatory signals. IL-10 treatment of DC promoted a suppression of allergen-specific Th2 cell responses. Moreover, Dp2-DC10 are able to promote T cell anergy associated with a reduction in the Th2 cytokine production. These results represent an important step forward to the prospective clinical application of Dp2-DC10 to modulate allergen-specific T cells responses in vivo. | en |
| format.extent | 3482563 bytes | - |
| format.mimetype | application/pdf | - |
| language.iso | en | en |
| subject | allergy | en |
| subject | Th2 | en |
| subject | dendritic cells | en |
| subject | IL-10 | en |
| subject | regulatory T cells | en |
| title | Potential role of IL-10-treated dendritic cells in the control of the immune response to allergens | en |
| type | Doctoral thesis | en |
| degree.name | Dottorato in biologia cellulare e molecolare | en |
| degree.level | Dottorato | en |
| degree.discipline | Facoltà di medicina e chirurgia | en |
| degree.grantor | Università degli studi di Roma Tor Vergata | en |
| date.dateofdefense | A.A. 2006/2007 | en |
| Appears in Collections: | Tesi di dottorato in medicina
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Description |
Size | Format |
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| PhD-Tesi Pacciani V.pdf | | 3400Kb | Adobe PDF | View/Open |
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