Functional skewing of bone marrow-derived dendritic cells by Th1- or Th2-inducing cytokines

Abstract

To investigate the functional difference of bone marrow (BM)-derived dendritic cells (DC), BM cells were cultured under three different cytokine conditions and the induced DC were temporarily designated as DC0, DC1, or DC2 cells. DC0 were induced by culture of BM cells with granulocyte–macrophage colony-stimulating factor (GMCSF) plus interleukin 3 (IL-3). DC1 were induced by culture with Th1-inducing cytokine (IL-12, gamma-interferon—IFN-γ) in addition to GMCSF plus IL-3. DC2 were induced by culture with Th2-inducing cytokine (IL-4) in addition to GMCSF plus IL-3. Flow cytometric analysis demonstrated that almost all DC0, DC1 and DC2 cells were stained with anti-CD11c, which reacts with a marker for DC cells. However, interestingly, DC0, DC1 and DC2 cells expressed different amounts of functional molecules on their cell surface. Namely, DC1 cells expressed the highest levels of MHC class I, class II, CD40, B7.1 and B7.2 compared with DC0 and DC2 cells. In terms of IL-12 production, DC1 cells showed enhanced production, while DC2 cells showed reduced production compared with DC0 cells. Moreover, it was shown that both DC0 and DC1 supported the differentiation of IFN-γ-producing Th1 cells, but not IL-4-producing Th2 cells from TCR-transgenic mouse naive Th cells. However, DC2 cells selectively enhanced the differentiation of IL-4-producing Th2 cells. These data strongly suggested that DC1 cells might be preferable antigen-presenting cells for application to immunotherapy.