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 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.
Feili-Hariri
Maryam
M
Division of Plastic Surgery, University of Pittsburgh, Scaife Hall, Suite 666, 3550 Terrace St., Pittsburgh, PA 15261, USA. haririmf@upmc.edu
Falkner
Dewayne H
DH
Morel
Penelope A
PA
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000187:drug effects; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D018664:Interleukin-12 / Q000096:biosynthesis; D019409:Interleukin-15 / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010641:Phenotype; D021122:Protein Subunits / Q000096:biosynthesis / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019409:Interleukin-15; D021122:Protein Subunits; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor