Polyriboinosinic polyribocytidylic acid (poly(I:C)) induces stable maturation of functionally active human dendritic cells.
For vaccination strategies and adoptive immunotherapy purposes, immature dendritic cells (DC) can be generated from adherent monocytes using GM-CSF and IL-4. Presently, the only clinically applicable method to induce stable maturation of DC is the use of supernatants of activated monocytes (monocyte-conditioned medium (MCM)). MCM contains an undefined mixture of cytokines and is difficult to standardize. Here we report that stable maturation of DC can be simply induced by the addition of polyriboinosinic polyribocytidylic acid (poly(I:C)), a synthetic dsRNA clinically applied as an immunomodulator. Poly(I:C)-treated DC show a mature phenotype with high expression levels of HLA-DR, CD86, and the DC maturation marker CD83. This mature phenotype is retained for 48 h after cytokine withdrawal. In contrast to untreated DC, poly(I:C)-treated DC down-regulate pinocytosis, produce high levels of IL-12 and low levels of IL-10, induce strong T cell proliferation in a primary allo MLR, and effectively present peptide Ags to HLA class I-restricted CTL. In conclusion, we present a simple methodology for the preparation of clinically applicable mature DC.
Verdijk
R M
RM
Department of Immunohematology and Blood Bank, Leiden University Medical Center, Leiden, The Netherlands. verdijk@rullf2.medfac.leidenuniv.nl
Mutis
T
T
Esendam
B
B
Kamp
J
J
Melief
C J
CJ
Brand
A
A
Goulmy
E
E
D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D000954:Antigens, Surface / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D015778:Minor Histocompatibility Antigens / Q000276:immunology / Q000378:metabolism; D008912:Minor Histocompatibility Loci / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism; D010873:Pinocytosis / Q000187:drug effects; D011070:Poly I-C / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
D000954:Antigens, Surface; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; C110615:HA-1 antigen; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D016753:Interleukin-10; D018664:Interleukin-12; D011070:Poly I-C