T细胞IL-7信号途径在Allo-HSCT后淋巴细胞增殖性疾病发病中作用机制研究

Allogeneic hematopoietic stem cell transplantation(Allo-HSCT) is one of the most effective therapeutic options for hematological malignancies. However, Epstein-Barr virus (EBV) associated post-transplantation lymphoproliferative disease (PTLD) is a serious and potentially life-threatening condition, which occur when the T cell immune response to EBV is ablated or severely compromised by immunosupression. Previous studies showed that EBV-specific T lymphocytes play a critical role in prevention and treatment of PTLD. Studies on the immunephenotypical and functional change of T cells in PTLD are scarce. Our previous studies showed that the levels of IL-7 in plasma were chronic decreased and the levels of T-BET and EOMES mRNA were lowered in PBMNC of PTLD patients than controls. We hypothesize that decreased IL-7 signaling in T cells may facilitate EBV reactivation and EBV-associated PTLD development. IL-7 may promote the survival and fuction of EBV-specific T lymphocytes. Therefore, the alteration of IL-7 signaling of T cells in PTLD deserves further studies.The purpose of current study is to investigate the alteration of IL-7 signaling of T cells in PTLD and the effect of activation of IL-7 signaling in EBV-specific T lymphocytes and the mechanism. The study could provide the the theoretical fundamental of EBV-specific T lymphocytes and IL-7 treatment in conditions of EBV reactivation and EBV-associated PTLD.

异基因造血干细胞移植（Allo-HSCT）是治疗恶性血液病有效的方法之一。EB病毒相关性移植后淋巴细胞增殖性疾病（PTLD）是导致患者死亡的严重并发症。研究表明，EB病毒特异性T细胞具有预防和控制PTLD的作用。然而，PTLD患者T细胞功能活性改变鲜有报道。我们前期发现EB病毒重激活和PTLD患者血浆IL-7水平持续低下，外周血单个核细胞T-BET、EOMES mRNA表达水平低。强烈提示T细胞IL-7信号途径改变可能是EB病毒重激活和EB病毒相关性PTLD发病的重要原因。IL-7可能通过延长病毒特异性细胞在体内生存。对 PTLD患者T细胞IL-7信号途径改变仍需进一步探索研究。本项目旨在研究EB病毒重激活和PTLD患者T细胞IL-7信号途径改变及激活本信号途径对EB病毒特异性T细胞功能活性的影响及机制，为EB病毒特异性T细胞与IL-7应用于预防与治疗EB病毒重激活和PTLD奠定理论基础。

异基因造血干细胞移植（Allo-HSCT）是治疗恶性血液病有效的方法之一。EB病毒相关性移植后淋巴细胞增殖性疾病（PTLD）是导致患者死亡的严重并发症。研究表明，EB病毒特异性T细胞具有预防和控制PTLD的作用。然而，PTLD患者T细胞功能活性改变鲜有报道。我们前期发现EB病毒重激活和PTLD患者血浆IL-7水平持续低下，外周血单个核细胞T-BET、EOMES mRNA表达水平低。强烈提示T细胞IL-7信号途径改变可能是EB病毒重激活和EB病毒相关性PTLD发病的重要原因。IL-7可能通过延长病毒特异性细胞在体内生存。对 PTLD患者T细胞IL-7信号途径改变仍需进一步探索研究。本项目研究了EB病毒重激活和PTLD患者T细胞IL-7信号途径改变及激活本信号途径对EB病毒特异性T细胞功能活性的影响及机制。通过采用B85-8细胞株培养上清感染获得供体B淋巴母细胞株，体外采用无血清培养基及白介素2、白介素7和白介素15及供体B淋巴母细胞株反复刺激培养获得EB病毒特意性T细胞，获得的病毒特异性T细胞在体外体内均有特异性杀伤活性。为EB病毒特异性T细胞与IL-7应用于预防与治疗EB病毒重激活和PTLD奠定理论基础。