Rabbit antithymocyte globulin (Thymoglobulin®) impairs the thymic output of both conventional and regulatory CD4+ T cells after allogeneic hematopoietic stem cell transplantation in adult patients
Rabbit antithymocyte globulin (Thymoglobulin®) impairs the thymic output of both conventional and regulatory CD4+ T cells after allogeneic hematopoietic stem cell transplantation in adult patients
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DOI：
10.3324/haematol.2012.067611
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发表时间：
2013-01-01
期刊：
影响因子：
--
通讯作者：
Thiel, Andreas
中科院分区：
文献类型：
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作者：
Na, Il-Kang;Wittenbecher, Friedrich;Thiel, Andreas
兔抗胸腺细胞球蛋白- genzyme （TM）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-健酶（TM）对胸腺功能的影响尚未得到很好的研究。采用多色流式细胞术分析同种异体造血干细胞移植后6个月内接受兔抗胸腺细胞球蛋白- genzyme （TM）治疗（n=12）或未接受治疗（n=8）的成人患者常规T细胞和调节性T细胞的动力学。在同种异体造血干细胞移植后的6个月内，接受兔抗胸腺细胞球蛋白- genzyme （TM）治疗的患者，常规和调节性CD4 T细胞的近期胸腺移行(CD45RA（+) CD31(+)）水平几乎检测不到，而CD4(+) CD45RA-记忆T细胞受到的影响较小，但其水平也显著低于未接受兔抗胸腺细胞球蛋白- genzyme （TM）治疗的患者。兔抗胸腺细胞球蛋白- genzyme （TM）在体外诱导人胸腺细胞凋亡和细胞溶解，其细胞毒作用大于兔抗胸腺细胞球蛋白-费森尤斯（TM）。兔抗胸腺细胞球蛋白- genzyme （TM）联合调理方案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细胞的持续耗竭会带来感染和移植物抗宿主病的高风险。我们的数据表明，使用兔抗胸腺细胞球蛋白- genzyme （TM）治疗的患者可以从胸腺保护治疗中获益，并且将该产品与其他兔抗胸腺细胞球蛋白制剂或淋巴细胞消耗化合物进行比较的试验将提供信息。(C) 2013 Ferrata Storti基金会。这是一篇开放获取的论文。doi: 10.3324 / haematol.2012.067611
Rabbit antithymocyte globulin-Genzyme (TM) 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 (TM) 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 (TM) during the first 6 months after allogeneic hematopoietic stem cell transplantation. Patients treated with rabbit antithymocyte globulin-Genzyme (TM) had almost undetectable levels of recent thymic emigrants (CD45RA(+) CD31(+)) of both conventional and regulatory CD4 T 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 (TM). In vitro, rabbit antithymocyte globulin-Genzyme (TM) induced apoptosis and cytolysis of human thymocytes, and its cytotoxic effects were greater than those of rabbit antithymocyte globulin-Fresenius (TM). Rabbit antithymocyte globulin-Genzyme (TM) 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 (TM) 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. (C) 2013 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2012.067611