Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells.
Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells.
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DOI：
10.1182/blood.v95.8.2484.008k01_2484_2490
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发表时间：
2000-04
期刊：
影响因子：
20.3
通讯作者：
M. Arpinati;C. Green;S. Heimfeld;Jill E. Heuser;C. Anasetti
中科院分区：
文献类型：
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作者：
M. Arpinati;C. Green;S. Heimfeld;Jill E. Heuser;C. Anasetti
从粒细胞集落刺激因子（G-CSF）动员的供体获得的外周血干细胞（PBSC）越来越多地用于同种异体移植。尽管移植T细胞的剂量高出10倍，但PBSC接受者发生急性移植物抗宿主病（GVHD）的比例并不比骨髓接受者高。来自G-CSF处理的实验动物的T细胞优先产生IL-4和IL-10，Th 2应答的特征性细胞因子，其与GVHD诱导能力降低相关。我们假设G-CSF动员的外周血干细胞含有抗原呈递细胞，这些细胞可以刺激T淋巴细胞产生Th 2细胞因子。根据树突状细胞（DC）分别诱导幼稚T细胞分化为Th 1和Th 2效应细胞的能力，已经在人类中描述了两种不同的树突状细胞（DC）谱系，DC 1和DC 2。我们使用荧光显微镜计数DC 1和DC 2在外周血中的正常供体。每天10 - 16 μ g/kg的G-CSF治疗5天，外周血DC 2计数从中位数4.9 x 10（6）/L增加到24.8 x 10（6）/L（P =.0009），而DC 1计数没有变化。未经处理或G-CSF处理的供体的纯化DC 1诱导同种异体幼稚T细胞增殖，但新鲜DC 2是较差的刺激物。肿瘤坏死因子-α（TNF-α）激活的DC 1诱导同种异体初始T细胞产生IFN-γ，这是典型的Th 1应答，而TNF-α激活的DC 2诱导同种异体初始T细胞产生IL-4和IL-10，这是典型的Th 2应答。与骨髓移植相比，PBSC移植含有更高剂量的DC 2（中位数，2.4 x 10（6）/kg vs 0.5 x 10（6）/kg）（P =.006），而DC 1的剂量相当。因此，可以想象，移植G-CSF刺激的PBSC不会导致压倒性的急性GVHD，因为移植物主要含有Th 2诱导的DC。纯化的DC 2的连续转移可用于诱导造血干细胞移植或器官移植后的免疫偏离。（血。2000;95：2484-2490）
Peripheral blood stem cells (PBSC) obtained from granulocyte-colony stimulating factor (G-CSF)-mobilized donors are increasingly used for allogeneic transplantation. Despite a 10-fold higher dose of transplanted T cells, acute graft-versus-host disease (GVHD) does not develop in higher proportion in recipients of PBSC than in recipients of marrow. T cells from G-CSF-treated experimental animals preferentially produce IL-4 and IL-10, cytokines characteristic of Th2 responses, which are associated with diminished GVHD-inducing ability. We hypothesized that G-CSF-mobilized PBSC contain antigen-presenting cells, which prime T-lymphocytes to produce Th2 cytokines. Two distinct lineages of dendritic cells (DC) have been described in humans, DC1 and DC2, according to their ability to induce naive T-cell differentiation to Th1 and Th2 effector cells, respectively. We have used multicolor microfluorometry to enumerate DC1 and DC2 in the peripheral blood of normal donors. G-CSF treatment with 10 to 16 microg/kg per day for 5 days increased peripheral blood DC2 counts from a median of 4.9 x 10(6)/L to 24.8 x 10(6)/L (P =.0009), whereas DC1 counts did not change. Purified DC1, from either untreated or G-CSF treated donors, induced the proliferation of allogeneic naive T cells, but fresh DC2 were poor stimulators. Tumor necrosis factor-alpha (TNF-alpha)-activated DC1 induced allogeneic naive T cells to produce IFN-gamma, which is typical of Th1 responses, whereas TNF-alpha-activated DC2 induced allogeneic naive T cells to produce IL-4 and IL-10, which are typical of Th2 responses. PBSC transplants contained higher doses of DC2 than marrow transplants (median, 2.4 x 10(6)/kg versus 0.5 x 10(6)/kg) (P =.006), whereas the dose of DC1 was comparable. Thus, it is conceivable that transplantation of G-CSF-stimulated PBSC does not result in overwhelming acute GVHD because the graft contains predominantly Th2-inducing DC. Adoptive transfer of purified DC2 may be exploited to induce immune deviation after transplantation of hematopoietic stem cells or organ allografts. (Blood. 2000;95:2484-2490)