IFN-γ对造血干细胞移植后肺部GVHD的作用

Effects of IFN-γ on Pulmonary GVHD after Allo-Hematopoietic Stem Cell Transplantation

目的:探讨IFN-γ对造血干细胞移植后肺部GVHD的作用。方法:应用C57BL/6J和B6D2F1小鼠通过造血干细胞移植(HSCT)建立小鼠GVHD模型。根据移植的方式将小鼠分为3组:同基因HSCT组(C57BL/6J→C57BL/6J),异基因HSCT组(C57BL/6J→B6D2F1)及IFN-γ-/-异基因HSCT组(IFN-γ-/-C57BL/6J→B6D2F1)。移植后分析比较3组小鼠生存期、aGVHD临床评分及肺组织病理,检测肺泡灌洗液中总细胞数及小鼠IFN-γ水平。结果:同基因移植组小鼠第42天全部存活,无aGVHD临床症状。异基因移植组小鼠有aGVHD表现,24 d生存率大于50%,GVHD临床评分高于同基因移植组。在移植后第28天肺组织病理可见肺泡出血及淋巴细胞浸润。IFN-γ-/-异基因移植组小鼠出现致死性aGVHD表现,14 d内小鼠全部死亡,GVHD临床评分第1周就高达6.7±0.83,明显高于异基因移植组,小鼠肺组织发生严重的aGVHD病理改变,其支气管肺泡灌洗液中总细胞数在移植后第1周较其他两组明显增高,但其血清中IFN-γ含量明显低于异基因移植组及同基因移植组(P<0.05)。结论:供者来源的IFN-γ对造血干细胞移植后肺组织起重要的免疫保护作用。

Objective： To explore the effects of IFN-γ on pulmonary GVHD after hematopoietic stem cell transplantation（ HSCT）. Methods： The mouse GVHD models were established by using C57BL/6 J,B6D2F1 mice and different HSCT. According to HSCT modes,the mice were divided into 3 groups： syngeneic HSCT group（ C57BL/6 J→C57 BL/6 J）,allogeneic HSCT group（ C57BL/6 J → B6D2F1） and IFN-γ^-/-allogeneic HSCT group（ IFN-γ^-/-→C57BL/6 J→ B6D2F1）. The survival time,GVHD clinical seore,pulmonary pathologic changes in 3 groups were compared and analyzed,and the total cell count in BALF and IFN-γ level in serum were detected in 3 groups after transplantation. Results： The mice in syngeneic HSCT group all survived at day 42 after transplantation without GVHD symptoms in lung,the GVHD clinical score was low. The mice in allogeneic HSCT group survived at day 24 after transplantation（ survial rate 〉50%）,the GVHD clinical score was higher than that in syngeneic HSCT group,the pathologic changes in lung did not serious,though the GVHD presentation was observed,but the olveola bleeding and lymphocyte infiltration in lung tissue were observed at day 28 after transplantation. The mice in IFN-γ^-/-allogeneic HSCT group all died of lethal GVHD within 14 days after transplantation,the GVHD clinical score reached to 6. 7 ± 0. 83 at 1 st week after tansplantation,which was significantly higher than that in syngeneic and allogeneic HSCT groups. At1 st week after transplantation,the serious GVHD pathological changes occured in lung tissue,total cell count in BALF significanty increased,compared with syngeneic and allogeneic HSCT groups,but IFN-γ level in serum was significantly lower than that in syngeneic and allogeneic HSCT groups（ P〈0. 05）. Conclusion： Donor-derived IFN-γ plays an important immunoprotective role for lung tissue after HSCT.