T‐cell‐mediated and antigen‐dependent differentiation of human monocyte into different dendritic cell subsets: a feedback control of Th1/Th2 responses

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 inter‐leukin‐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. FASEB J. 22, 3370–3379 (2008)