It is well established that human monocytes differentiate into dendritic cells (DCs) when cultured with certain cytokine cocktails, such as granulocyte-macrophage colony-stimulating factor and interleukin-4. Conversely, it is not completely established which cell population synthesizes the cytokines required for monocyte differentiation and how their secretion is regulated. We show that on specific activation T cells induce the differentiation into DCs of antigen-presenting and bystander monocytes. Monocytes exposed to cytokines released by Th1 and Th0 lymphocytes differentiate into DCs with a reduced antigen uptake and antigen presentation capacity. Moreover, these DCs show a limited capacity to induce Th1 polarization of naive T cells but are capable of priming interleukin-10-secreting T cells. Conversely, DCs derived from monocytes sensing cytokines released by Th2 lymphocytes are antigen-presenting-cell (APC) endowed with a marked Th1 polarization capacity. Monocytes are corecruited with lymphocytes in chronic inflammation sites; thus our results suggest that functionally different DCs can be generated in environments characterized by the prevalent release of Th1-, Th0-, or Th2-associated cytokines. Because the APC capacities of these DCs have opposite functional consequences, a contribution in the regulation of the ongoing immune response by monocyte-derived inflammatory DCs is envisaged.—Mariotti, S., Sargentini, V., Marcantonio, C., Todero, E., Teloni, R., Gagliardi, M. C., Ciccaglione, A. R., Nisini, R. T-cell-mediated and antigen-dependent differentiation of human monocyte into different dendritic cell subsets: a feedback control of Th1/Th2 responses.