Human monocyte-derived dendritic cells induce naive T cell differentiationinto 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 D C maturation determine the capacity of DCs to generate polarized immune res ponses. In this study, we show that the ability of human monocyte-derived D Cs (myeloid DC1) to promote T helper type 1 (Th1) or Th2 differentiation wa s also found to be critically dependent on stimulator/responder ratio. At a low ratio (1:300), mature DCs that have been differentiated after inflamma tory (Staphylococcus aureus Cowan 1 or lipopolysaccharide) or T cell-depend ent (CD40 ligand) stimulation induced naive T cells to become Th2 (interleu kin [IL]-4(+), IL-5(+), interferon gamma) effectors. Th2 differentiation wa s dependent on B7-CD28 costimulation and enhanced by OX40-OX40 Ligand inter actions. However, high DCT cell ratio (1:4) favored a mixed Th1/Th2 cell de velopment. Thus, the fact that the same DC lineage stimulates polarized Th1 or Th2 responses may be relevant since it allows the antigen-presenting ce lls to initiate an appropriate response for the signal received at the peri pheral 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.