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 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.
Dipartimento Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Sabrina
S
Mariotti
Valeria
V
Sargentini
Cinzia
C
Marcantonio
Emiliano
E
Todero
Raffaela
R
Teloni
Maria Cristina
MC
Gagliardi
Anna Rita
AR
Ciccaglione
Roberto
R
Nisini
D000938:Antigen-Presenting Cells / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology*; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D010587:Phagocytosis; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*
D016207:Cytokines