Caux C, Massacrier C, Dezutter-Dambuyant C, Vanbervliet B, Jacquet C, Schmitt D, Banchereau J
Schering-Plough, Laboratory for Immunologic Research, Dardilly, France.
J Immunol. 1995 Dec 1;155(11):5427-35.
Earlier studies have concluded that fresh Langerhans cells (LC) are able to capture and process native Ags, whereas cultured LC have lost these functions while acquiring the capacity to prime naive T cells. Herein we studied the functions of human dendritic/Langerhans cells (d-Lc) generated in vitro by culturing CD34+ hemopoietic progenitor cells in the presence of granulocyte-macrophage CSF (GM-CSF) + TNF-alpha. Less than 50 d-Lc were found to strongly stimulate the proliferation of 2.5 x 10(4) allogeneic naive CD4+ T cells. Furthermore, six to 50 d-Lc induced half-maximal proliferation of naive syngeneic CD4+ cord blood T cells, in the presence of picomolar concentrations of superantigens. During the alloreaction, the CD4+ T cells were expanded up to 100-fold within two successive stimulation cycles with the same d-Lc, and the recovered T cells were specific for the d-Lc alloantigen. HLA-matched tetanus toxoid (TT)-specific T cell clones were found to proliferate in response to TT presented by CD1a+ d-Lc. Finally, electron microscopy demonstrated that CD1a+ d-Lc were able to capture an Ag (gold-labeled Igs) through receptor-mediated endocytosis. Thus, in vitro generated d-Lc can prime naive T cells and process native Ags, a property that might eventually prove useful for priming Ag-specific naive T cells for cellular immunotherapy.
早期研究得出结论，新鲜的朗格汉斯细胞（LC）能够捕获和处理天然抗原，而培养的LC在获得激活初始T细胞的能力时已丧失这些功能。在此，我们研究了通过在粒细胞-巨噬细胞集落刺激因子（GM-CSF）+肿瘤坏死因子-α存在下培养CD34+造血祖细胞体外生成的人树突状/朗格汉斯细胞（d-Lc）的功能。发现少于50个d-Lc就能强烈刺激2.5×10⁴个同种异体初始CD4⁺T细胞的增殖。此外，在皮摩尔浓度的超抗原存在下，6至50个d-Lc可诱导同基因初始CD4⁺脐血T细胞增殖达到半数最大效应。在同种异体反应过程中，CD4⁺T细胞在与相同的d-Lc进行两个连续刺激周期内可扩增至100倍，并且回收的T细胞对d-Lc同种异体抗原有特异性。发现HLA匹配的破伤风类毒素（TT）特异性T细胞克隆可响应由CD1a⁺d-Lc呈递的TT而增殖。最后，电子显微镜显示CD1a⁺d-Lc能够通过受体介导的内吞作用捕获一种抗原（金标记的免疫球蛋白）。因此，体外生成的d-Lc能够激活初始T细胞并处理天然抗原，这一特性最终可能被证明对激活抗原特异性初始T细胞用于细胞免疫治疗有用。
