Tiefenthaler Martin, Hofer Susanne, Ebner Susanne, Ivarsson Lennart, Neyer Susanne, Herold Manfred, Mayer Gert, Fritsch Peter, Heufler Christine
Department of Nephrology, University of Innsbruck, Innsbruck, Austria.
Nephrol Dial Transplant. 2004 Mar;19(3):553-60. doi: 10.1093/ndt/gfg594.
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.
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.
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.
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.
据报道，高剂量（10⁻⁶ - 10⁻⁸ M）的他克莫司（FK506）可在发育中的树突状细胞（DC）中诱导2型辅助性T细胞（Th2）促进功能。我们使用治疗剂量（2.4 x 10⁻⁹ M）的他克莫司来研究其对人单核细胞来源的DC的影响。
我们比较了未处理和经他克莫司处理的未成熟和成熟DC的T细胞激活能力、表面标志物表达、T细胞和DC细胞因子谱以及编码一组DC功能相关分子的基因转录情况。
经他克莫司处理的成熟DC的T细胞刺激能力降低。虽然DC的白细胞介素（IL）-12产生受损，但它们并未促进Th2发育，因为经他克莫司处理的DC激活的T细胞产生的干扰素（IFN）-γ、IL-4和IL-10较少。T细胞激活标志物CD69的上调和IL-2的产生受损。此外，经他克莫司处理的DC产生的IP-10（CXCL10）较少，已知其参与同种异体移植排斥反应。其他与DC功能相关的分子保持不变。
他克莫司治疗降低了DC刺激T细胞的能力，DC来源的IP-10（CXCL10）和IL-12产生受损可能在他克莫司的免疫抑制作用中起作用。
