The Journal of Experimental Medicine
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Published online 7 August 2000.
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© The Rockefeller University Press, 0022-1007/2000/8/405/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 3, August 7, 2000 405-412

Original Article

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



Hiroyuki Tanakaa, Christian E. Demeurea, Manuel Rubioa, Guy Delespessea, and Marika Sarfatia

a 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
University of Montreal, Allergy Research Laboratory (M4211-K), Centre de Recherche du CHUM, Notre-Dame Hospital, 1560 Sherbrooke St. East, Montreal, Quebec H2L 4M1, Canada.514-896-4753514-281-6000 ext. 6632

sarfatm{at}poste.umontreal.ca

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 DC1) 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.

Key Words: Th1 • Th2 • dendritic cells • B7-OX40 • interleukin 4

Abbreviations used in this paper: CTLA, cytolytic T lymphocyte–associated Ag; DC, dendritic cell; DC1, human monocyte-derived DC; DC2, plasmacytoid DC; iDC, immature DC; mDC, mature DC; SAC, Staphylococcus aureus Cowan 1.

© 2000 The Rockefeller University Press


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