Tanaka J, Mori A, Ota S, Yamamoto Y, Kobayashi S, Hashino S, Asaka M, Imamura M
Hematology and Oncology, Hokkaido University School of Medicine, Sapporo, Japan.
Eur J Haematol. 2000 May;64(5):333-9. doi: 10.1034/j.1600-0609.2000.90142.x.
The CD28 responsive element binding complex (CD28RC) has an important role in transducing CD28/B7 costimulatory signals. Using electrophoretic mobility-shift assay (EMSA), we have analyzed the binding activity of CD28RC in the mixed lymphocyte culture (MLC) using peripheral blood mononuclear cells (PBMC) obtained from the patients before and after allogeneic bone marrow transplantation (allo-BMT). The binding activity of CD28RC was low in MLCs using PBMC from patients without acute GVHD and it was also low in MLCs using PBMC from patients without chronic GVHD (cGVHD). In contrast, this activity in patients with cGVHD was estimated to be high. The relative values of CD28RC in comparison with third party MLCs were significantly higher in MLCs using PBMC from patients with cGVHD than those in MLCs using PBMC from patients without GVHD (0.55+/-0.31 versus 0.23+/-0.12, respectively, n = 10, p = 0.05). IL-2 concentrations in the MLC medium from patients without GVHD were undetectable; however, a detectable level of IL-2 was present in MLC medium from a patient with extensive cGVHD. These data were interpreted to suggest that the CD28 costimulatory pathway was specifically activated against recipient antigen in allo-BMT patients with GVHD. In other words, it was suggested that the CD28 costimulatory pathway was specifically suppressed in allo-BMT patients without GVHD, and this suppression might contribute immunological tolerance after allo-BMT.
CD28反应元件结合复合物（CD28RC）在转导CD28/B7共刺激信号中起重要作用。我们采用电泳迁移率变动分析（EMSA），利用从异基因骨髓移植（allo-BMT）前后患者获取的外周血单个核细胞（PBMC），分析了混合淋巴细胞培养（MLC）中CD28RC的结合活性。在使用无急性移植物抗宿主病（GVHD）患者的PBMC进行的MLC中，CD28RC的结合活性较低，在使用无慢性GVHD（cGVHD）患者的PBMC进行的MLC中，其结合活性也较低。相反，cGVHD患者的这种活性估计较高。与第三方MLC相比，使用cGVHD患者PBMC的MLC中CD28RC的相对值显著高于使用无GVHD患者PBMC的MLC（分别为0.55±0.31和0.23±0.12，n = 10，p = 0.05）。无GVHD患者的MLC培养基中检测不到IL-2浓度；然而，一名患有广泛cGVHD的患者的MLC培养基中存在可检测水平的IL-2。这些数据被解释为表明，在患有GVHD的allo-BMT患者中，CD28共刺激途径针对受体抗原被特异性激活。换句话说，提示在无GVHD的allo-BMT患者中，CD28共刺激途径被特异性抑制，这种抑制可能有助于allo-BMT后的免疫耐受。
