In vitro treatment of dendritic cells with tacrolimus: impaired T-cell activation and IP-10 expression

Nephrol Dial Transplant. 2004 Mar;19(3):553-60. doi: 10.1093/ndt/gfg594.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Chemokine CXCL10
  • Chemokines, CXC / genetics
  • Chemokines, CXC / metabolism*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Lymphocyte Activation / drug effects*
  • RNA, Messenger / genetics
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • Tacrolimus / pharmacology*

Substances

  • Chemokine CXCL10
  • Chemokines, CXC
  • Cytokines
  • Immunosuppressive Agents
  • RNA, Messenger
  • Tacrolimus