Ferlazzo G, Wesa A, Wei W Z, Galy A
Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
J Immunol. 1999 Oct 1;163(7):3597-604.
Dendritic cells (DC) can be generated in vitro from monocytes (M-DC) or from CD34+ hemopoietic progenitor cells (CD34-DC) but their precursors are not equivalent cells, prompting a comparison of the functional capacities of these APC. Both types of DCs established from the same individuals using the same cytokines displayed a comparable phenotype of mature DC (CD1a+, CD83+, CD86+, CD4+, HLA-DR++, CD14-, CD15- ) and were equally potent stimulators of allogeneic T cell proliferation, being both more powerful than immature M-DCs. An autologous panel of APCs produced in HLA-A2+ individuals, including CD34-DC, M-DC, monocytes, and EBV-lymphoid cell line was comparatively evaluated for presentation of the Erb-B2 peptide E75 to a CTL line. After short exposures (5 h) to E75-loaded APCs, similar levels of intracellular IFN-gamma were induced in Ag-specific CD8+ T cells regardless of APC type. In sustained cultures (4-14 days), more Ag-specific T cells were obtained when peptide was presented on CD34-DC (p < 0.05) rather than on M-DC, EBV-lymphoid cell lines, or monocytes, and these effects were dose-dependent. Activated T cells expressed 4-1BB, and the presence of 4-1BB-Ig fusion protein partially blocked Ag-specific CD8+ cell activation after CD34-DC or M-DC presentation. Our results show that 34-DC have a preferential capacity to activate CD8+ T cells and that this property is not strictly correlated to their ability to induce allogeneic T cell proliferation but due to mechanisms that remain to be defined.
树突状细胞(DC)可在体外由单核细胞(M-DC)或CD34+造血祖细胞(CD34-DC)生成,但它们的前体细胞并非等同细胞,这促使人们对这些抗原呈递细胞(APC)的功能能力进行比较。使用相同细胞因子从同一个体建立的两种类型的DC显示出相似的成熟DC表型(CD1a+、CD83+、CD86+、CD4+、HLA-DR++、CD14-、CD15-),并且都是同种异体T细胞增殖的同等有效的刺激物,两者都比未成熟的M-DC更强大。对在HLA-A2+个体中产生的一组自体APC,包括CD34-DC、M-DC、单核细胞和EBV淋巴母细胞系,进行了针对向CTL系呈递Erb-B2肽E75的比较评估。在短暂暴露于负载E75的APC(5小时)后,无论APC类型如何,在抗原特异性CD8+T细胞中诱导出相似水平的细胞内干扰素-γ。在持续培养(4 - 14天)中,当肽呈递在CD34-DC上时(p < 0.05),比呈递在M-DC、EBV淋巴母细胞系或单核细胞上获得更多的抗原特异性T细胞,并且这些效应是剂量依赖性的。活化的T细胞表达4-1BB,并且4-1BB-Ig融合蛋白的存在部分阻断了CD34-DC或M-DC呈递后抗原特异性CD8+细胞的活化。我们的结果表明,34-DC具有优先激活CD8+T细胞的能力,并且这种特性与其诱导同种异体T细胞增殖的能力并非严格相关,而是由于仍有待确定的机制。