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Originally published online as doi:10.1189/jlb.1104631 on June 16, 2005

Published online before print June 16, 2005
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(Journal of Leukocyte Biology. 2005;78:656-664.)
© 2005 by Society for Leukocyte Biology

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

Maryam Feili-Hariri*,{dagger},1, Dewayne H. Falkner{dagger} and Penelope A. Morel{dagger},{ddagger},2

* Departments of Surgery
{dagger} Immunology, and
{ddagger} Medicine, University of Pittsburgh School of Medicine, Pennsylvania

1Correspondence: Department of Surgery, Division of Plastic Surgery, University of Pittsburgh, Scaife Hall, Suite 666, 3550 Terrace St., Pittsburgh, PA 15261. E-mail: haririmf{at}upmc.edu

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 low 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)-{gamma}, 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-{gamma}. In contrast, the GM + IL-15 DCs induced higher IFN-{gamma} 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.

Key Words: T cell activation • costimulation • IL-12p70 • IFN-{gamma}




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