Efficient Presentation of House Dust Mite Allergen Der p 2 by Monocyte‐Derived Dendritic Cells and the Role of β2 Integrins

Monocyte-derived dendritic cells (MDDC) are potent antigen-presenting cells (APC). The APC functions of MDDC in allergy were examined. MDDC presentation of the major house dust mite allergen Der p 2 resulted in 4-12-fold higher T-cell proliferation and markedly higher IFN-gamma and IL-5 production than PBMC cultures. Comparable T-cell proliferation was obtained with 10-fold fewer MDDC than purified monocytes. MDDC cultured from adherent cells, or CD14+, CD11b+ or Percoll-purified monocytes were comparable in presenting soluble Ag, and in stimulating allogeneic MLR. Importantly, MDDC presentation of Der p 2 resulted in both Th1 and Th2 stimulation, although MDDC are known to produce high levels of IL-12 and stimulate biased Th1 responses. The basis for the potent APC function of MDDC was further examined. MDDC were found to be highly phagocytic. Immunoprecipitation studies showed markedly elevated ICAM-1 expression but > 10-fold reduction in LFA-1 expression on MDDC compared with monocytes. Monoclonal antibody (MoAb)-blocking experiments showed that ICAM-LFA-1 interaction was essential for MDDC stimulation of Der p 2-specific T-cell proliferative responses. These results show that the use of MDDC as APC provides a simple, sensitive and versatile method for detecting T-cell responses to allergens and that the strong phagocytic capability and the increased ICAM-1 expression of MDDC contribute significantly to their Ag presentation potency.