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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1685-1693.
Prepublished online as a Blood First Edition Paper on May 5, 2005May 10, 2005; DOI 10.1182/blood-2004-12-4738.
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Submitted December 13, 2004
Accepted April 28, 2005
Negative feed back regulation of T helper type 1 (Th1)/Th2 cytokine balance via dendritic cell and natural killer T cell interactions
Keita Minami, Yoshiki Yanagawa, Kazuya Iwabuchi, Nobuo Shinohara, Toru Harabayashi, Katsuya Nonomura, and Kazunori Onoe*
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; Department of Urology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
Department of Urology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
* Corresponding author; email: kazunori{at}igm.hokudai.ac.jp.
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 (Th1)/Th2-cytokine environment on DC induction of NKT cell-mediated cytokine production in mice. Pretreatment of myeloid DCs with Th1 or Th2 cytokines, interleukin (IL)-4 or interferon (IFN)- , led to the enhanced production of reciprocal cytokines by NKT cells (e.g. IL-4 pretreatment led to the enhanced production of Th1 cytokines) in vitro and in vivo. Thus, the recognition of Th1 or Th2 cytokines by DCs acts as a negative feedback loop to maintain Th1/Th2-cytokine balance via NKT cell functions. Using this data, we manipulated cytokine levels and innate cytolytic activity in vivo to increase an anti-tumor 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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