Takabayashi Maki, Kanamori Heiwa, Takasaki Hirotaka, Yamaji Satoshi, Koharazawa Hideyuki, Taguchi Jun, Tomita Naoto, Fujimaki Katsumichi, Fujisawa Shin, Maruta Atsuo, Ishigatsubo Yoshiaki
Department of Internal Medicine and Clinical Immunology, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
Exp Hematol. 2005 Feb;33(2):251-7. doi: 10.1016/j.exphem.2004.10.009.
We monitored cytokine-secreting cells using an enzyme-linked immunospot (ELISPOT) assay in a prospective study to assess the cytokine network after transplantation.
Peripheral blood mononuclear cells were collected from 23 patients who received allogeneic stem cell transplantation, from before the preconditioning regimen to 56 days after transplantation. The number of interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha)-secreting cells were measured by ELISPOT assay. For IL-4 and IFN-gamma, in vitro stimulation with phorbol 12-myristate 13-acetate and phytohemagglutinin was performed.
The frequency of IL-4-secreting cells was significantly higher in five patients receiving peripheral blood stem cell transplantation (PBSCT) than that in 18 patients who received bone marrow transplantation (BMT). Based on IFN-gamma and TNF-alpha release, there was a trend toward a decrease in the number of cytokine-secreting cells in PBSCT compared with BMT. Furthermore, patients who did not develop acute graft-vs-host disease (GVHD, n=5) showed a significantly higher number of IL-4-secreting cells compared with those who developed acute GVHD (n=18). Both IFN-gamma-secreting cells and TNF-alpha-secreting cells showed a trend to increase in number in patients with acute GVHD. In patients who received reduced-intensity stem cell transplantation (n=7) compared with conventional stem cell transplantation (n=16), there was a large number of cytokine-secreting cells detected by IL-4 and IFN-gamma release.
These results are consistent with the hypothesis that IL-4-producing cells inhibit the development of acute GVHD. In addition, the increased percentage of IL-4-secreting cells may be responsible for the unexpected low incidence of acute GVHD in PBSCT, despite the presence of large numbers of mature T cells in the donor infusion.
在一项前瞻性研究中，我们使用酶联免疫斑点（ELISPOT）检测法监测细胞因子分泌细胞，以评估移植后的细胞因子网络。
收集23例接受异基因干细胞移植患者从预处理方案前至移植后56天的外周血单个核细胞。通过ELISPOT检测法测定白细胞介素-4（IL-4）、干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）分泌细胞的数量。对于IL-4和IFN-γ，用佛波醇12-肉豆蔻酸酯13-乙酸酯和植物血凝素进行体外刺激。
5例接受外周血干细胞移植（PBSCT）的患者中IL-4分泌细胞的频率显著高于18例接受骨髓移植（BMT）的患者。基于IFN-γ和TNF-α的释放，与BMT相比，PBSCT中细胞因子分泌细胞的数量有减少的趋势。此外，未发生急性移植物抗宿主病（GVHD，n = 5）的患者与发生急性GVHD的患者（n = 18）相比，IL-4分泌细胞的数量显著更高。急性GVHD患者中IFN-γ分泌细胞和TNF-α分泌细胞的数量均有增加的趋势。与接受传统干细胞移植（n = 16）的患者相比，接受低强度干细胞移植（n = 7）的患者中，通过IL-4和IFN-γ释放检测到大量细胞因子分泌细胞。
这些结果与产生IL-4的细胞抑制急性GVHD发生的假说一致。此外，尽管供体输注中有大量成熟T细胞，但IL-4分泌细胞百分比的增加可能是PBSCT中急性GVHD意外低发生率的原因。
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