1. In vitro treatment of dendritic cells with tacrolimus: impaired T-cell activation and IP-10 expression
- Author
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Peter Fritsch, Susanne Ebner, Lennart Ivarsson, Manfred Herold, Gert Mayer, Martin Tiefenthaler, Susanne Neyer, S Hofer, and Christine Heufler
- Subjects
T-Lymphocytes ,medicine.medical_treatment ,T cell ,Cell Culture Techniques ,chemical and pharmacologic phenomena ,Lymphocyte Activation ,Tacrolimus ,Interferon ,medicine ,Humans ,CXCL10 ,RNA, Messenger ,Interleukin 4 ,Transplantation ,business.industry ,Interleukin ,Dendritic Cells ,Chemokine CXCL10 ,Interleukin 10 ,surgical procedures, operative ,Cytokine ,medicine.anatomical_structure ,Nephrology ,Immunology ,Cancer research ,Cytokines ,business ,Chemokines, CXC ,Immunosuppressive Agents ,medicine.drug - 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.
- Published
- 2004
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