Journal
BLOOD
Volume 106, Issue 5, Pages 1685-1693Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2004-12-4738
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The ability of extracellular stimuli to modulate dendritic cell (DC) activation of natural killer T (NKT) cells was not well understood. We investigated the effects of the T helper type 1 (Thl)/Th2-cytokine environment on DC induction of NKT cell-mediated cytokine production in mice. Pretreatment of myeloid DCs with Thl or Th2 cytokines, interleukin (IL)-4 or inter-feron (IFN)-gamma, led to the enhanced production of reciprocal cytokines by NKT cells leg, IL-4 pretreatment led to the enhanced production of Thl cytokines) in vitro and in vivo. Thus, the recognition of Thl or Th2 cytokines by DCs acts as a negative feedback loop to maintain Thl/Th2-cytokine balance via NKT cell functions. Using these data, we manipulated cytokine levels and innate cytolytic activity in vivo to increase an antitumor response. This is the first description of a novel regulation system governing Th1/Th2 cytokine balance involving DCs and NKT cells.
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