Functional maturation of dendritic cells by exposure to CD40L transgenic tumor cells, fibroblasts or keratinocytes.
Tumor antigen pulsed dendritic cells (DCs) can induce anti-tumor immunity. We studied strategies for the reliable generation of such a tumor vaccine by functional maturation of DCs via interaction of CD40 with its ligand (CD40L, CD154). Exposure of immature DCs to CD40L transgenic cells, soluble recombinant human CD40L molecules or lipopolysaccharide induced expression of the co-stimulatory molecules, CD80 and CD86, and supported an allogeneic mixed leukocyte reaction. In contrast, the release of IL-12, an important mediator of anti-tumor immunity, and antigen-specific expansion and IFNgamma secretion of lymphocytes, was strongly triggered only by DCs exposed to CD40L transgenic cells.
Felzmann
T
T
Children's Cancer Research Institute, St. Anna Children's Hospital, Kinderspitalgasse 6, 1090, Vienna, Austria. felzmann@ccri.univie.ac.at
Buchberger
M
M
Lehner
M
M
Printz
D
D
Kircheis
R
R
Wagner
E
E
Gadner
H
H
Holter
W
W
D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D023201:CD40 Ligand / Q000235:genetics* / Q000276:immunology* / Q000494:pharmacology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D019496:Cancer Vaccines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma