FK506 in the maturation of dendritic cells.
OBJECTIVE
FK506 (tacrolimus) is a potent immunosuppressive agent that inhibits interleukin-2 (IL-2) and interferon-g production by CD4+ cells. The effect of this agent on dendritic cells (DCs), the highly professional antigen-presenting cells for T-cells, has not been completely defined. We investigated the effect of FK506 on DC differentiation from monocytes, and on the shift from immature to mature immunophenotypes.


METHODS
DCs were generated in vitro from monocytes of healthy donors. Cells were exposed to lipopolysaccharide (LPS) and two doses of FK506, with variations in time of exposure and sequence of FK506 and LPS addition. Immunophenotype analysis in immature and mature DCs under FK506 treatment was performed by flow cytometry at the end of cell culture. The Student's t-test was used for statistical analyses.


RESULTS
FK506 did not affect dendritic cell generation or viability. There were no changes in cell surface markers with addition of FK506 at physiologic concentrations (10 ng/mL). We found a decrease in CD1a median fluorescence intensity (MFI) and an increase in percentage of CD86-positive cells with lengthy exposure (6 days) to FK506 at 5000 ng/mL. In the sequential study, 5000 ng/mL FK506 before LPS addition resulted in a significant decrease in CD1a MFI and in the percentage of cells co-expressing CD83 and CD86.


CONCLUSIONS
Our results indicate that lengthy exposure to 5000 ng/mL FK506 modified the expression of some DC-cell surface markers, maintaining DCs in a low maturity stage.
Cos
Joan
J
Centre de Transfusió i Banc de Teixits, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain. jcos@hg.vhebron.es
Villalba
Teresa
T
Parra
Rafael
R
Gallardo
Dominique
D
Bilbao
Itxarone
I
Margarit
Carlos
C
Massuet
Lluís
L
D015703:Antigens, CD / Q000032:analysis; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology*
D015703:Antigens, CD; D007166:Immunosuppressive Agents; D016559:Tacrolimus