HUMAN DENDRITIC CELLS, ALLERGY AND ASTHMA

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Dendritic cells (DC) are considered to be the major antigen (Ag) presenting cells. The biology of these cells and their role in the human immune response in both health and disease have not been studied in depth due to the difficulty in obtaining a significant number of these cells from peripheral blood and the inability to culture these cells in vitro. Recent experiments carried out by the PI and by others indicate it is feasible to obtain a large number of DC from peripheral blood with improved isolation procedures and the addition of GM-CSF and IL-4. House dust mite (HDM)-induced asthma is a major public health problem and the allergic response is considered to be initiated by exposure to low doses of HDM allergens over a prolonged period. Ag presenting cells play critical roles in allergy disease development. Results from this laboratory and others showed that with the same Ag the two professional Ag presenting cell types DC and B cells induced T helper cell subsets differently. DC favor Th1 whereas B cells at low Ag concentrations favor Th2 responses. The skewed response of the Th2 subset is a cause for allergic diseases. To examine the basis for this opposite stimulatory effects on T helper subsets by DC and B cells, the following specific aims are proposed: (I) to isolate DC from peripheral blood to characterize the factors influencing their survival and proliferating potential; (2) to determine the mechanism for this difference in T helper subset responses in asthma patients and normal individuals; and (3) to determine the T cell epitopes recognized by the two different T helper subsets generated by Ag presentation by DC or B cells. The proposed experiments will provide new insights to the role of DC in asthma and may provide a rational basis for designing immunotherapy for allergic disorders.