Department of Hematology, Oncology and Tumor Immunology, Charité, Berlin, Germany.
Haematologica. 2013 Jan;98(1):23-30. doi: 10.3324/haematol.2012.067611. Epub 2012 Jul 16.
Rabbit antithymocyte globulin-Genzyme™ is used to prevent graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Common disadvantages of treatment are infectious complications. The effects of rabbit antithymocyte globulin-Genzyme™ on thymic function have not been well-studied. Multicolor flow cytometry was used to analyze the kinetics of conventional and regulatory T cells in adult patients treated (n=12) or not treated (n=8) with rabbit antithymocyte globulin-Genzyme™ during the first 6 months after allogeneic hematopoietic stem cell transplantation. Patients treated with rabbit antithymocyte globulin-Genzyme™ had almost undetectable levels of recent thymic emigrants (CD45RA(+)CD31(+)) of both conventional and regulatory CD4T cells throughout the 6 months after allogeneic hematopoietic stem cell transplantation whereas CD4(+)CD45RA-memory T cells were less affected, but their levels were also significantly lower than in patients not treated with rabbit antithymocyte globulin-Genzyme™. In vitro, rabbit antithymocyte globulin-Genzyme™ induced apoptosis and cytolysis of human thymocytes, and its cytotoxic effects were greater than those of rabbit antithymocyte globulin-Fresenius™. Rabbit antithymocyte globulin-Genzyme™ in combination with a conditioning regimen strongly impairs thymic recovery of both conventional and regulatory CD4(+) T cells. The sustained depletion of conventional and regulatory CD4(+)T cells carries a high risk of both infections and graft-versus-host disease. Our data indicate that patients treated with rabbit antithymocyte globulin-Genzyme™ could benefit from thymus-protective therapies and that trials comparing this product with other rabbit antithymocyte globulin preparations or lymphocyte-depleting compounds would be informative.
兔抗胸腺细胞球蛋白-酶合物™用于预防异基因造血干细胞移植后的移植物抗宿主病。治疗的常见缺点是感染并发症。兔抗胸腺细胞球蛋白-酶合物™对胸腺功能的影响尚未得到很好的研究。多色流式细胞术用于分析接受（n=12）或未接受（n=8）兔抗胸腺细胞球蛋白-酶合物™治疗的成年患者在异基因造血干细胞移植后 6 个月内常规和调节性 T 细胞的动力学。在异基因造血干细胞移植后 6 个月内，接受兔抗胸腺细胞球蛋白-酶合物™治疗的患者几乎检测不到常规和调节性 CD4T 细胞的近期胸腺迁出细胞（CD45RA（+）CD31（+）），而 CD4（+）CD45RA-记忆 T 细胞受影响较小，但水平也明显低于未接受兔抗胸腺细胞球蛋白-酶合物™治疗的患者。体外，兔抗胸腺细胞球蛋白-酶合物™诱导人胸腺细胞凋亡和细胞溶解，其细胞毒性作用大于兔抗胸腺细胞球蛋白-弗雷森纽斯™。兔抗胸腺细胞球蛋白-酶合物™与预处理方案联合强烈损害常规和调节性 CD4（+）T 细胞的胸腺恢复。常规和调节性 CD4（+）T 细胞的持续耗竭既存在感染风险，也存在移植物抗宿主病风险。我们的数据表明，接受兔抗胸腺细胞球蛋白-酶合物™治疗的患者可能受益于胸腺保护治疗，并且比较该产品与其他兔抗胸腺细胞球蛋白制剂或淋巴细胞耗竭化合物的试验将提供信息。
