Negative feedback regulation of T helper type 1 (Th1)/Th2 cytokine balance via dendritic cell and natural killer T cell interactions.
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)-gamma, led to the enhanced production of reciprocal cytokines by NKT cells (eg, 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 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.
Minami
Keita
K
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan.
Yanagawa
Yoshiki
Y
Iwabuchi
Kazuya
K
Shinohara
Nobuo
N
Harabayashi
Toru
T
Nonomura
Katsuya
K
Onoé
Kazunori
K
D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D025461:Feedback, Physiological; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000032:analysis / Q000276:immunology / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013433:Sulfoglycosphingolipids / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D013433:Sulfoglycosphingolipids; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma