异基因造血干细胞移植后共刺激分子LIGHT／HVEM的表达与GVHD的关系

The expression of LIGHT and HVEM in T lymphocytes post aIIo-HSCT and its relation to the development of GVHD

目的探讨异基因造血干细胞移植（allo-HSCT）后共刺激分子LIGHT和HVEM的表达与移植物抗宿主病（GVHD）发生的关系。方法26例allo-HSCT患者中，预处理方案采用环磷酰胺＋足叶乙甙＋全身照射11例，采用氟达拉滨＋阿糖胞苷＋白消安12例，采用环磷酰胺3例。移植时，输注单个核细胞（5．89±3．36）×10^8／kg，CD34^＋细胞（3．29±1．29）×10^6／kg。预防急性GVHD（aGVHD）的方案采用环孢素A＋短程甲氨蝶呤＋吗替麦考酚酯，HLA半相合及非血缘关系者加用抗胸腺细胞球蛋白。GVHD的诊断与分级采用西雅图标准。在预处理前、移植后15d、发生aGVHD时及aGVHD经治疗好转后分别采集患者外周血2ml，采用三色流式细胞术进行检测，同时以15名健康志愿者的血液标本作为正常对照。结果所有患者均获得造血功能重建，移植物均完全植活。移植后共发生aGVHD9例，发生率为35％，其中Ⅲ～Ⅳ度者3例，8例经治疗后好转，1例治疗无效死亡；发生慢性GVHD（cGVHD）7例，发生率为26．9％。患者预处理前和移植后15d及正常人外周血T淋巴细胞几乎不表达LIGHT，组成性表达HVEM；发生GVHD时，LIGHT表达显著上调，HVEM表达下调；GVHD好转后，LIGHT和HVEM的表达恢复正常。移植后158时，发生aGVHD者LIGHT的表达高于未发生aGVHD者，而HVEM的表达较低（P〈0．05）。Ⅲ～Ⅳ度aGVHD者LIGHT的表达明显高于I～II度者（P〈0．05）。结论LIGHT／HVEM在allo-HSCT后GVHD的发生和发展过程中起重要作用，通过监测该共刺激分子的表达对aGVHD的发生有一定预示作用。

Objective To explore the relationship between the expression of LIGHT/HVEM in patients after allo-HSCT and the development of GVHD. Methods The expression of LIGHT and HVEM in T lymphocytes was detected by FACS Calibur. Results All patients achieved engraftment and hematopoiesis reconstitution, aGVHD occurred in 9 of 26 patients （34. 6 %） with grade III-IV aGVHD in 3 cases. Seven cases developed cGVHD （26. 9 % ）. LIGHT was not expressed in T lymphocytes from healthy donors and patients without GVHD, while constitutive expression of HVEM was detected. When aGVHD occurred, the expression levels of LIGHT in T lymphocytes were significantly increased, while those of HVEM decreased. After GVHD was controlled, the expression levels of those co-stimulators went back to normal. On the day 15 after transplantation, the expression of LIGHT in T lymphoeytes of patients with aGVHD later was significantly higher, while that of HVEM lower than in those without aGVHD. The patients with aGVHD of grades III-IV demonstrated higher LIGHT expression than in those with aGVHD of grades I - II. Conclusion The expression of LIGHT and HVEM might be involved in the development of GVHD after aIlo-HSCT and could be used as one of the＇useful indicators in predicting aGVHD.