协同刺激因子在移植物抗宿主病发生中作用的初步研究

Effect of costimulatory moleculars on graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

目的 探讨协同刺激因子（CM）在异基因造血干细胞移植（allo-HSCT）相关移植物抗宿主病（GVHD）中的作用.方法根据预处理方案不同,将21例行 allo-HSCT的血液病和实体瘤患者分为A组（NST组）和B组（清髓性HSCT组）;所有患者在移植前后不同时间,应用流式细胞术（FCM）检测外周血CD＋4T细胞表面CM（CD28、CD80、CD152）的表达;用短串联重复序列聚合酶链反应（STR-PCR）方法检测微卫星嵌合体形成.结果21例患者移植后均获得造血功能重建,经STR-PCR检测均转为混合嵌合体（MC）或完全嵌合体（CC）;不同预处理方案GVHD发生率差异无统计学意义（x2=3.711,P=0.144）;COX回归分析结果显示：CD4＋;CD152＋能明显影响GVHD发生（x2=13.128,P＜0.0001）;术后,外周血T细胞表面CD4＋;CD28＋、CD4＋;CD80＋表达逐渐增高,GVHD时达高峰,经过治疗和控制GVHD后,逐渐下降;而T细胞表面CD4＋CD152＋表达则逐渐降低,GVHD时最低,经治疗和控制GVHD后,又逐渐上升.结论清髓性HSCT和NST的GVHD发生率无差别;T细胞表面CM的表达与GVHD发生有关,并且在清髓性HSCT和NST的表达不同;B7-CD28/CD152共刺激途径在GVHD发生中起重要作用.

Objective To explore the effect of costimulatory moleculars expressed peripheral CD4＋ T lymphocyts on graft-versus-host disease（GVHD） after allogeneic hematopoietic stem cell transplantation （alloHSCT）. Methods 21 patients who suffered of hematology diseases or malignant solid tumors were underwent allo-HSCT and 10 normal individuals were enrolled in the study. The levels of CD28, CD80 and CD152expressions on peripheral CD4＋ T lymphocytes were detected by FCM in different time（before allo-HSCT, 7 day,14 day, 21 day, 30 day after allo-HSCT, thetime of GVHD and the time after GVHD treated）. STR-PCR was used to detect micro-satellites chimeras forming. Results All 21 patients achieved engraftment. By STR-PCR assay, 12 cases formed complete chimeras （CC） and 9 cases formed mixed chimeras （MC）. A multivariate COX survival function modle analysis showed： CD4 CD152 was independent prognostic factors for GVHD （x2=13.128,P 〈0.0001）. Patients with GVHD demonstrated higher CD4＋ CD28＋, CD4＋ CD80＋ and CD4＋ CD152＋ T cell levels than those without GVHD （P 〈0.01）; patients with aGVHD demonstrated higher than those with cGVHD （P 〈0.05）and without GVHD （P 〈0.05）; Patients with GVHD demonstrated lower CD4＋ CD152＋ T cell level than those without GVHD （P 〈0.01）; the same result occured between aGVHD and cGVHD and without GVHD.Conclusion The incidence of GVHD between NST and traditional HSCT have no difference. B7-CD28/CD152 costimulatory pathway plays a critical role in the development of GVHD.