Tanaka J, Imamura M, Kasai M, Sakurada K
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Leuk Lymphoma. 1995 Sep;19(1-2):27-32. doi: 10.3109/10428199509059660.
In this study, we have investigated cytokine (IL-1 beta, IL-2, IL-5, IL-6, IFN-gamma, TNF-alpha) and T cell surface molecule (IL-2 receptor, CD28, CTLA-4) gene expression in two way mixed lymphocyte cultures (MLC) enhanced by concanavalin A (ConA) to assess whether this is a useful predictive method for severe graft-versus-host disease (GVHD) and graft failure in allogeneic bone marrow transplantation (allo BMT) patients. Our present study revealed increased mRNA expression of IL-2, IL-5 and IFN-gamma using this assay in patients with delayed engraftment followed by graft failure and patients who developed grade III acute GVHD. Elevated IL-2 and IFN-gamma levels in MLC medium were also observed in these patients. Concerning T cell surface molecule gene expression in our modified MLC, IL-2 receptor gene expression was not altered so much in allo BMT patients, however, CD28 and CTLA-4 gene expression were elevated in patients with graft failure and severe acute GVHD. The elevated expression of cytokines (IL-2, IL-5 and IFN-gamma) and T cell surface molecules (CD28 and CTLA-4) mRNA in our modified MLC, in patients who developed severe lethal transplantation-related complications may suggest an important role for these molecules in inducing a strong alloresponse. Therefore, the detection of increased gene expression of those molecules, in our modified MLC system, appeared to be useful for predicting transplantation-related complications in allo BMT patients. In addition, this modified MLC assay may also be useful for the selection of the most compatible related and unrelated donors.
在本研究中，我们调查了在伴刀豆球蛋白A（ConA）增强的双向混合淋巴细胞培养（MLC）中细胞因子（白细胞介素-1β、白细胞介素-2、白细胞介素-5、白细胞介素-6、干扰素-γ、肿瘤坏死因子-α）和T细胞表面分子（白细胞介素-2受体、CD28、细胞毒性T淋巴细胞相关抗原4）的基因表达，以评估这是否是预测异基因骨髓移植（allo BMT）患者严重移植物抗宿主病（GVHD）和移植物失败的有用方法。我们目前的研究显示，在植入延迟随后出现移植物失败的患者以及发生III级急性GVHD的患者中，使用该检测方法可观察到白细胞介素-2、白细胞介素-5和干扰素-γ的mRNA表达增加。在这些患者中还观察到MLC培养基中白细胞介素-2和干扰素-γ水平升高。关于我们改良的MLC中T细胞表面分子基因表达，在allo BMT患者中白细胞介素-2受体基因表达变化不大，然而，在移植物失败和严重急性GVHD患者中CD28和细胞毒性T淋巴细胞相关抗原4基因表达升高。在发生严重致命的移植相关并发症的患者中，我们改良的MLC中细胞因子（白细胞介素-2、白细胞介素-5和干扰素-γ）和T细胞表面分子（CD28和细胞毒性T淋巴细胞相关抗原4）mRNA的表达升高，可能表明这些分子在诱导强烈的同种异体反应中起重要作用。因此，在我们改良的MLC系统中检测这些分子基因表达的增加，似乎有助于预测allo BMT患者的移植相关并发症。此外，这种改良的MLC检测方法也可能有助于选择最匹配的相关和无关供体。
