受者特异性产生干扰素γ细胞与急性移植物抗宿主病的关系

Relationship between the IFN-γ producing cells specific for recipient and acute graft versus host dis- ease

目的 研究异基因造血干细胞移植（allo—HSCT）中针对受者特异性产生干扰素γ细胞（IFN-γPC）与急性移植物抗宿主病（aGVHD）的关系。方法 以37例HLA相合的同胞allo-HSCT患者为研究对象，将移植前供者、移植后患者外周血单个核细胞（PBMNC）分别作为反应细胞（RC），移植前受者PBMNC作为异基因刺激细胞（allo-SC），在混合淋巴细胞反应后用酶联免疫斑点法检测针对受者特异性IFN-γPC，分析其与aGVHD的关系。结果 allo-HSCT前检测受者特异性IFN-γPC水平，移植后发生aGVHD组显著高于无aGVHD组（P〈0．01）；供者针对受者特异性IFN-γPC≥20／2×10^5RC时，发生Ⅱ～Ⅳ度aGVHD的比例显著高于〈20／2×10^5RC组（P〈0．05）。aGVHD发生时患者针对移植前受者特异性IFN-γPC水平显著高于移植前相应供者针对受者的水平（P〈0．05）；亦显著高于aGVHD患者针对移植前供者的水平（P〈0．01）。移植后14天（＋14天）和＋28天时，aGVHD组受者特异性IFN-γPC水平均显著高于无aGVHD组（P值均〈0．01）。aGVHD患者经过免疫抑制剂治疗7d后，受者特异性IFN-γPC较aGVHD发生时显著降低（P〈0．05）。结论 受者特异性IFN-γPC的水平能够反映allo-HSCT前后的同种异体反应，有助于临床aGVHD的预测、诊断和监测。

Objective To study the relationship between the IFN-γproducing cell specific for recipient （IFN-γ-PCSR） in allogeneic stem cell transplantation （allo-HSCT） and acute graft versus host disease （aGVHD）. Methods In 37 consecutive HLA-identical sibling allo-HSCT pairs, peripheral blood mononuclear cells （PBMNC） from donors before allo-HSCT and recipients after allo-HSCT were taken as responder ceils （RC）,and PBMNC from recipients before allo＋HSCT as allogeneic stimulator cells（allo-SC） in mixed lymphocyte reaction （MLR）. IFN-γ-PCSR in PBMNC were assayed using enzyme linked immunospot assay （ELISPOT）. Results Pretransplantation frequencies of IFN-γ-PCSR in donor PBMNC were significantly higher in aGVHD group than in non-aGVHD group （P 〈0.01 ）and IFN-γPCSRs （ ≥20/2 × 105RC） were significantly associated with the occurrence of grade Ⅱ - Ⅳ GVHD （P 〈 0.05 ）. Compared with that before allo-HSCT, IFN-γ PCSR in PBMNC of aGVHD patients was significantly increased （P 〈 0. 05 ）. When PBMNC from aGVHD patients reacted with donor PBMNC, the IFN-γ PC was significantly lower than that with recipient PBMNC before allo-HSCT. Longitudinal analysis of IFN-γ PCSR following allo-HSCT showed tF, at compared with that in patients without aGVHD, the IFN-γPCSR were significantly higher in patients with that in aGVHD on day ＋ 14（P 〈0.01 ） and day ＋ 28 （P 〈0.01 ）, respectively. After immunosuppressive therapy for 7 days, IFN-γPC declined significantly （P 〈 0.05）. Conclusion The recipient-specific IFN-γ PC is closely correlated with the alloresponse during allo-HSCT and may be helpful for the prediction, diagnosis and monitoring of aGVHD.