D'Costa S, Hurwitz J L
Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Bone Marrow Transplant. 2002 Apr;29(7):553-6. doi: 10.1038/sj.bmt.1703428.
Rigorous T cell depletion methods can now be used to reduce the risk of graft-versus-host disease (GVHD) associated with allogeneic, hematopoietic stem cell transplantation (HSCT). However, full T cell depletion is also associated with a significant risk of graft failure. Here we hypothesize that engraftment failures after T cell-depleted HSCT may be due, in part, to the absence of GVHD prophylaxis. To test this hypothesis, we used a haploidentical mouse model to systematically measure the effects of immunosuppressive drug treatments and anti-T cell antibodies on engraftment. Results showed that engraftment was supported in all animals when hosts were pre-treated with anti-T cell antibodies, but donor chimerism was significantly improved when hosts were also treated with prednisone. Interestingly, when hosts received only pre-HSCT prednisone treatments, engraftment was not improved; when hosts received only post-HSCT prednisone (initiated near the time of irradiation), the animals became extremely ill. Results therefore demonstrated the need for both pre- and post-HSCT prednisone treatments as a means to ensure engraftment without morbidity in all host animals.
现在可以使用严格的T细胞清除方法来降低与异基因造血干细胞移植（HSCT）相关的移植物抗宿主病（GVHD）风险。然而，完全T细胞清除也与移植失败的重大风险相关。在这里，我们假设T细胞清除后的HSCT移植失败可能部分归因于缺乏移植物抗宿主病预防措施。为了验证这一假设，我们使用半相合小鼠模型系统地测量免疫抑制药物治疗和抗T细胞抗体对移植的影响。结果表明，当宿主用抗T细胞抗体进行预处理时，所有动物的移植均得到支持，但当宿主也接受泼尼松治疗时，供体嵌合率显著提高。有趣的是，当宿主仅接受HSCT前泼尼松治疗时，移植没有改善；当宿主仅接受HSCT后泼尼松治疗（在照射时开始）时，动物病情极其严重。因此，结果表明需要在HSCT前后都进行泼尼松治疗，作为确保所有宿主动物移植成功且无发病的一种手段。
