The contributing role of circulating human dendritic cell (DC) populations and basophils in the presentation and augmentation of Th2 responses remains to be determined. The present study aimed at elucidating the functional role of CD1c+ myeloid DCs (mDCs), CD123+ plasmacytoid DCs (pDCs), monocyte-derived DCs and basophils in allergen presentation and Th2 activation. By coculturingPhleum pratense(Phl p)-pulsed CD1c+ mDCs, CD123+ pDCs, monocyte-derived DCs and basophils with autologous CD4+ effector memory T cells, we assessed T-cell proliferation as well as the frequency of interleukin-4- and interferon-γ-producing T cells. Interestingly, a Th2-stimulating ability was observed for Phl p-challenged CD1c+ mDCs and monocyte-derived DCs, while CD123+ pDCs and basophils did not affect the Th-balance. In addition, both Phl p-pulsed CD1c+ mDCs and monocyte-derived DCs stimulated increased T-cell proliferation compared to basophils and CD123+ pDCs. Together, these results point to a prominent role for circulating CD1c+ mDCs in allergen presentation and augmentation of Th2 responses, making them promising therapeutic targets for Type I hypersensitivity reactions.