Th2 polarization by Der p 1-pulsed monocyte-derived dendritic cells is dueto the allergic status of the donors

The polarization of the immune response toward a Th2 or a Th1 profile can b e mediated by dendritic cells (DCs) following antigen presentation and inte raction with T cells. Costimulatory molecules such as CD80 and CD86 express ed by DCs, the polarizing cytokine environment during DC-T-cell interaction , and also the nature of the antigen are critical in the orientation of the immune response. In this study, the effect of the cysteine protease Der p 1, one of the major allergens of the house dust mite Dermatophagoides, pter onyssinus, on these different parameters was evaluated comparatively on mon ocyte-derived DCs obtained from healthy donors, from pollen-sensitive patie nts, or from patients sensitive to Dermatophagoides pteronyssinus. Results showed that Der p 1 induced an increase in CD86 expression only on DCs from house dust mite-sensitive patients. This was also associated with a higher capacity to induce T-cell proliferation, a rapid increase in the productio n of proinflammatory cytokines, tumor necrosis factor-alpha and interleukin (IL)-1 beta, and the type 2 cytokine IL-10. No changes in the release of I L-12 p70 were induced by Der p 1. Finally, purified T cells from house dust mite-sensitive patients stimulated by autologous Der p 1-pulsed DCs prefer entially produced IL-4 rather than interferon-gamma. These effects were abo lished ih the presence of the inactive precursor of Der p 1 (ProDer p 1). T aken together, these data suggest that DCs from house dust mite-sensitive p atients, in contrast to DCs from healthy donors and from pollen-sensitive p atients, exposed to Der p 1 play a pivotal role in the enhancement of the T h2 response associated with the allergic reaction developed in response to house dust mite exposure.