Shimizu K, Fujii S, Fujimoto K, Kawa K, Yamada A, Kawano F
Department of Immunology, Kurume University School of Medicine, Fukuoka, Japan.
J Leukoc Biol. 2000 Nov;68(5):633-40.
The macrolide lactone, tacrolimus (FK506), is utilized in bone marrow transplantation (BMT) to prevent graft-versus-host disease (GVHD). In the current study, we evaluated the ability of FK506 to modify the function of dendritic cells (DCs) derived from CD34+ hematopoietic progenitor cells (HPCs). Comparable to DCs obtained in the absence of FK506, DCs cultured in the presence of FK506 (FK-DCs) had higher expression of CD1a+ and formed a greater number of DC colonies. Despite the same expression of costimulatory molecules, FK-DCs displayed a reduced capacity to stimulate an allogeneic T cell response, and showed significantly lower interleukin (IL)-12 production. While normal DCs pulsed with the exogenous antigen, keyhole limpet hemocyanin (KLH) induced specific Th1-like interferon-gamma(IFN-gamma) producing CD4+ T cell line, FK-DCs induced Th2-like interleukin-4 (IL-4) producing CD4+ T cell line. These data demonstrate the ability of FK506 to induce Th2-promoting function in developing DCs.
大环内酯类内酯他克莫司（FK506）用于骨髓移植（BMT）以预防移植物抗宿主病（GVHD）。在本研究中，我们评估了FK506调节源自CD34 +造血祖细胞（HPC）的树突状细胞（DC）功能的能力。与在不存在FK506的情况下获得的DC相比，在存在FK506的情况下培养的DC（FK-DC）具有更高的CD1a +表达并形成更多的DC集落。尽管共刺激分子的表达相同，但FK-DC刺激同种异体T细胞反应的能力降低，并且白细胞介素（IL）-12的产生明显降低。当用外源性抗原钥孔戚血蓝蛋白（KLH）脉冲的正常DC诱导产生特异性Th1样干扰素-γ（IFN-γ）的CD4 + T细胞系时，FK-DC诱导产生Th2样白细胞介素-4（IL-4）的CD4 + T细胞系。这些数据证明了FK506在发育中的DC中诱导Th2促进功能的能力。
