Tada Y, Asahina A, Nakamura K, Miyazono K, Tomura M, Fujiwara H, Tamaki K
Department of Dermatology, University of Tokyo, Tokyo, Japan.
Eur J Immunol. 2001 Jan;31(1):294-300. doi: 10.1002/1521-4141(200101)31:1<294::AID-IMMU294>3.0.CO;2-D.
Transforming growth factor (TGF)-beta is an immunosuppressive agent that is efficacious in suppressing a wide variety of cell-mediated immune responses. However, the direct effect of this cytokine on Langerhans cells (LC) has not been clarified. In this study, we examined its modulatory effects on the expression of co-stimulatory molecules and LC IL-12 production. A highly purified population of LC (>95%) was prepared from BALB/c mouse skin by the panning method using anti-I-Ad mAb. Semiquantitative reverse transcription-PCR analysis showed that LC express TGF-beta receptor II mRNA. Interestingly, TGF-beta1 enhanced IL-12 p40 production of anti-CD40/IFN-gamma-stimulated LC, despite its down-regulatory effect on CD40 expression. A bioassay using an IL-12-dependent T cell line demonstrated the correlation of the IL-12 p40 level with the bioactivity of IL-12. More importantly, it was found that in contrast to TGF-beta, granulocyte/macrophage colony-stimulating factor (GM-CSF) strikingly inhibits IL-12 production of anti-CD40/IFN--stimulated LC and that the level of LC IL-12 production is determined by the relative amounts of TGF-beta1 and GM-CSF. Taken together, these results suggest that the two cytokines produced in the skin microenvironment, namely TGF-beta and GM-CSF, exert their important effects on LC function by regulating the secretion of IL-12, a cytokine influencing the Th1-Th2 balance.
转化生长因子（TGF）-β是一种免疫抑制剂，在抑制多种细胞介导的免疫反应方面具有疗效。然而，这种细胞因子对朗格汉斯细胞（LC）的直接作用尚未明确。在本研究中，我们检测了其对共刺激分子表达和LC白细胞介素-12（IL-12）产生的调节作用。通过使用抗I-Ad单克隆抗体的淘选法从BALB/c小鼠皮肤中制备了高度纯化的LC群体（>95%）。半定量逆转录-聚合酶链反应分析表明LC表达TGF-β受体II mRNA。有趣的是，尽管TGF-β1对CD40表达有下调作用，但它增强了抗CD40/干扰素-γ刺激的LC的IL-12 p40产生。使用依赖IL-12的T细胞系进行的生物测定证明了IL-12 p40水平与IL-12生物活性的相关性。更重要的是，发现与TGF-β相反，粒细胞/巨噬细胞集落刺激因子（GM-CSF）显著抑制抗CD40/干扰素-γ刺激的LC的IL-12产生，并且LC的IL-12产生水平由TGF-β1和GM-CSF的相对量决定。综上所述，这些结果表明皮肤微环境中产生的两种细胞因子，即TGF-β和GM-CSF，通过调节IL-12的分泌对LC功能发挥重要作用，IL-12是一种影响Th1-Th2平衡的细胞因子。
