Interferon-alpha and granulocyte-macrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigen-presenting cells.
The diverse roles of interferon-alpha (IFN-alpha) in regulating the immune response to infectious agents suggested that it might affect dendritic cell (DC) development. Peripheral blood mononuclear cells cultured with IFN-alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) developed a dendritic morphology and expressed high levels of the class I and II human leukocyte antigens (HLA), B7 co-stimulatory molecules, adhesion proteins, and CD40. Elevated DC expression of B7-2 and HLA-DR was observed with increasing IFN-alpha concentrations up to 5000 U/mL. The effects of IFN-alpha on DC immunophenotype were not reversed by adding neutralizing antibodies against interleukin-4 (IL-4) or tumor necrosis factor alpha to the cell cultures or by eliminating lymphocytes from the cultures. The addition of IFN-alpha to cultures containing optimal concentrations of IL-4 and GM-CSF significantly increased the B7-2 and HLA-DR levels above those present on DCs grown in two cytokines. The DCs generated with IFN-alpha and GM-CSF were potent antigen-presenting cells in allogeneic mixed leukocyte reactions. They also were capable of taking up, processing, and presenting tetanus toxin to autologous T lymphocytes. These results demonstrate an important role for IFN-alpha in the generation of DCs with potent antigen-presenting capabilities from peripheral blood monocytes.
Paquette
R L
RL
Department of Medicine, the University of California at Los Angeles, 90095-1678, USA. paquette@ucla.edu
Hsu
N C
NC
Kiertscher
S M
SM
Park
A N
AN
Tran
L
L
Roth
M D
MD
Glaspy
J A
JA
D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000502:physiology; D007959:Lymphocyte Culture Test, Mixed; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor