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THE USE OF PLASMACYTOID DENDRITIC CELLS FOR ALLERGENICITY SCREENING OF CHEMICALS.
Ayehunie, S., Lamore, S., Snell, M., Klausner, M., Sheasgreen, J.
MatTek Corporation, Ashland, MA, USA.
Presented at The American Association of Immunologists, Boston, MA, May 12-16 (2006).
Keywords: Allergenicity, Antigen microenvironment, CD34+, CD86, Chemical allergens, Cytokine cocktail, Dendritic cells, Guinea pig maximization test (GPMT), High throughput screening (HTS), Irritancy, Langerhan cells, Local lymph node assay (LLNA), PDC, Plasmacytoid, Plasmacytoid dendritic cells, pDC
Endpoints: CD86, Co-stimulating molecule, Cytokine, ELISA assays, FACS analysis, Local Lymph node assay (LLNA), RT-PCR
Materials Tested: Balsam of peru, Bandowski’s base, Cinnamaldehyde, Cobalt chloride, DMSO, Dinitrochlorobenzene, Ethanol, Fluorescein isothiocyanate, Gllutaraldehyde, Hydroquinone, Neomycin sulfate, Nickel sulfate, Potassium dichromate, Potassium hydroxide, Propylene glycol, Sodium dodecyl sulfate, Tween 20, dinitrobenzene sulfonic acid, p-phenylene diamine
Summary:
Development of a predictive test system to screen chemicals for their allergenicity potential has enormous significance.
Since dendritic cells/Langerhans cells (DC/LC) are the first cells responsible for sampling skin surfaces for changes in the antigen microenvironment, MatTek scientists investigated whether phenotypic and functional changes to a subset of DC, plasmacytoid dendritic cells (pDC), could be used to identify allergens.
To achieve this goal, normal human DC were generated from CD34+ progenitor cells and were cryopreserved. Frozen DC were thawed and the pDC fraction (CD123+/CD11c-) was collected using FACS sorting.
The pDC were cultured, expanded, and pulsed with chemical allergens (n=12) or irritants (n=7).
Results showed that exposure of pDC (n=3 donors) to allergens induced an increase (> 1.5 fold) in surface expression of CD86 for 11 of the 12 allergens; however, 6 of 7 irritants did not result in increased CD86 expression. Based on these findings, a prediction model was developed with a sensitivity of 92%, specificity of 86%, and an accuracy of 89%.
In conclusion, increased expression of CD86 by pDC appears to serve as sensitive and specific marker for the identification of chemical allergens. Versus existing animal models, the assay is advantageous because high throughput screening of chemicals using cells of human origin is possible at low cost.
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Please go to Technical Paper TR-449 - it contains more recent pDC allergenicity information
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