In vitro treatment of dendritic cells with tacrolimus: impaired T-cell activation and IP-10 expression.
BACKGROUND
High doses (10(-6)-10(-8) M) of tacrolimus (FK506) were reported to induce a type-2 T-helper cell (Th2)-promoting function in developing dendritic cells (DC). We used a therapeutic dose (2.4 x 10(-9 )M) of tacrolimus to investigate its effect on human monocyte-derived DC.


METHODS
Using untreated and treated immature and mature DC we compared T cell-activating capacity, surface marker expression, T cell and DC cytokine profile and transcription of genes coding for a panel of DC function-related molecules.


RESULTS
Tacrolimus-treated mature DC had reduced T-cell stimulatory capacity. Although interleukin (IL)-12 production of DC was impaired, they did not promote Th2 development as T cells activated by tacrolimus-treated DC produced less interferon (IFN)-gamma, IL-4 and IL-10. The up-regulation of the T-cell activation marker CD69 and the production of IL-2 were impaired. In addition, tacrolimus-treated DC produced less IP-10 (CXCL10), which is known to be involved in allograft rejection. Other molecules related to DC function remained unchanged.


CONCLUSIONS
Tacrolimus treatment reduces the ability of DC to stimulate T cells and the impaired production of DC-derived IP-10 (CXCL10) and IL-12 might play a role in the immunosuppressive action of tacrolimus.
Tiefenthaler
Martin
M
Department of Nephrology, University of Innsbruck, Innsbruck, Austria.
Hofer
Susanne
S
Ebner
Susanne
S
Ivarsson
Lennart
L
Neyer
Susanne
S
Herold
Manfred
M
Mayer
Gert
G
Fritsch
Peter
P
Heufler
Christine
C
D018929:Cell Culture Techniques; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology*
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016559:Tacrolimus