Human monocyte-derived dendritic cells induce naive T cell differentiation into T helper cell type 2 (Th2) or Th1/Th2 effectors. Role of stimulator/responder ratio.
The subset of dendritic cells (DCs) and the nature of the signal inducing DC maturation determine the capacity of DCs to generate polarized immune responses. In this study, we show that the ability of human monocyte-derived DCs (myeloid DC(1)) to promote T helper type 1 (Th1) or Th2 differentiation was also found to be critically dependent on stimulator/responder ratio. At a low ratio (1:300), mature DCs that have been differentiated after inflammatory (Staphylococcus aureus Cowan 1 or lipopolysaccharide) or T cell-dependent (CD40 ligand) stimulation induced naive T cells to become Th2 (interleukin [IL]-4(+), IL-5(+), interferon gamma) effectors. Th2 differentiation was dependent on B7-CD28 costimulation and enhanced by OX40-OX40 ligand interactions. However, high DC/T cell ratio (1:4) favored a mixed Th1/Th2 cell development. Thus, the fact that the same DC lineage stimulates polarized Th1 or Th2 responses may be relevant since it allows the antigen-presenting cells to initiate an appropriate response for the signal received at the peripheral sites. Controlling the number and the rate of DC migration to the T cell areas in lymphoid tissues may be important for the therapeutic use of DCs.
Allergy Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CHUM), Notre-Dame Hospital, Montreal University, Montreal, Quebec H2L 4M1, Canada.
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H
Tanaka
C E
CE
Demeure
M
M
Rubio
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Delespesse
M
M
Sarfati
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D019891:Leukopoiesis; D008562:Membrane Glycoproteins; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D053278:OX40 Ligand; D011971:Receptors, Immunologic / Q000378:metabolism; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048069:Tumor Necrosis Factors
D018122:B7-1 Antigen; D018106:CD28 Antigens; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D011971:Receptors, Immunologic; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C089251:TNFSF4 protein, human; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D018664:Interleukin-12