PMID- 15961574 OWN - NLM STAT- MEDLINE DCOM- 20060111 LR - 20240109 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 78 IP - 3 DP - 2005 Sep TI - Polarization of naive T cells into Th1 or Th2 by distinct cytokine-driven murine dendritic cell populations: implications for immunotherapy. PG - 656-64 AB - 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. FAU - Feili-Hariri, Maryam AU - Feili-Hariri M AD - Division of Plastic Surgery, University of Pittsburgh, Scaife Hall, Suite 666, 3550 Terrace St., Pittsburgh, PA 15261, USA. haririmf@upmc.edu FAU - Falkner, Dewayne H AU - Falkner DH FAU - Morel, Penelope A AU - Morel PA LA - eng GR - CA73743/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20050616 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (B7-1 Antigen) RN - 0 (B7-2 Antigen) RN - 0 (Interleukin-15) RN - 0 (Protein Subunits) RN - 187348-17-0 (Interleukin-12) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - B7-1 Antigen/biosynthesis/drug effects MH - B7-2 Antigen/biosynthesis/drug effects MH - CD4-Positive T-Lymphocytes/drug effects/*immunology/metabolism MH - Cell Differentiation/drug effects/immunology MH - Cell Polarity/drug effects/immunology/physiology MH - Cells, Cultured MH - Dendritic Cells/*cytology/drug effects/*immunology MH - Female MH - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - *Immunotherapy MH - Interferon-gamma/biosynthesis/drug effects MH - Interleukin-12/biosynthesis MH - Interleukin-15/biosynthesis/immunology/pharmacology MH - Interleukin-4/biosynthesis/immunology/pharmacology MH - Mice MH - Mice, Inbred NOD MH - Mice, Inbred Strains MH - Mice, Transgenic MH - Phenotype MH - Protein Subunits/biosynthesis/drug effects MH - Th1 Cells/drug effects/*immunology MH - Th2 Cells/drug effects/*immunology EDAT- 2005/06/18 09:00 MHDA- 2006/01/13 09:00 CRDT- 2005/06/18 09:00 PHST- 2005/06/18 09:00 [pubmed] PHST- 2006/01/13 09:00 [medline] PHST- 2005/06/18 09:00 [entrez] AID - jlb.1104631 [pii] AID - 10.1189/jlb.1104631 [doi] PST - ppublish SO - J Leukoc Biol. 2005 Sep;78(3):656-64. doi: 10.1189/jlb.1104631. Epub 2005 Jun 16.