Polarization of naive T cells into Th1 or Th2 by distinct cytokine-driven murine dendritic cell populations: implications for immunotherapy

Dendritic cells (DCs) activate T cells and regulate their differentiation into T helper cell type 1 (Th1) and/or Th2 cells. To identify DCs with differing abilities to direct Th1/Th2 cell differentiation, we cultured mouse bone marrow progenitors in granulocyte macrophage‐colony stimulating factor (GM), GM + interleukin (IL)‐4, or GM + IL‐15 and generated three distinct DC populations. The GM + IL‐4 DCs expressed high levels of CD80/CD86 and major histocompatibility complex (MHC) class II and produced ow levels of IL‐12p70. GM and GM + IL‐15 DCs expressed low levels of CD80/CD86 and MHC class II. The GM + IL‐15 DCs produced high levels of IL‐12p70 and interferon (IFN)‐γ, whereas GM DCs produced only high levels of IL‐12p70. Naive T cells stimulated with GM + IL‐4 DCs secreted high levels of IL‐4 and IL‐5 in addition to IFN‐γ. In contrast, the GM + IL‐15 DCs induced higher IFN‐γ production by T cells with little or no Th2 cytokines. GM DCs did not induce T cell polarization, despite producing large amounts of IL‐12p70 following activation. A similar pattern of T cell activation was observed after in vivo administration of DCs. These data suggest that IL‐12p70 production alone, although necessary for Th1 differentiation, is not sufficient to induce Th1 responses. These studies have implications for the use of DC‐based vaccines in immunotherapy of cancer and other clinical conditions.