Interleukin 7 worsens graft-versus-host disease
Interleukin 7 worsens graft-versus-host disease
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DOI：
10.1182/blood-2002-04-1082
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发表时间：
2002-10-01
期刊：
影响因子：
20.3
通讯作者：
Mackall, CL
中科院分区：
文献类型：
--
作者：
Sinha, ML;Fry, TJ;Mackall, CL
受损的免疫重建已成为限制异基因骨髓移植(BMT)进展的临床问题的前沿。确定通过增加胸腺生成来增强免疫重建的治疗方法是解决这一问题的关键。白介素7(IL-7)是迄今发现的最有效的胸腺生成细胞因子。为了研究IL-7在异基因骨髓移植后免疫重建和移植物抗宿主病(GVHD)中的作用，我们将重组人IL-7(rhIL-7)在小鼠亲本体内注入F1模型。结果显示，重组人白介素7治疗降低了诱发GVHD临床症状和致死性GVHD所需的“阈值”T细胞剂量。对GVHD靶组织的组织学分析显示，在所研究的所有T细胞剂量下，rhIL-7增加了GVHD的炎症程度和组织损伤，但不改变受累器官的类型或靶器官内GVHD的组织学形态。此外，我们评估了在同种异体T细胞耗竭(TCD)和T细胞全骨髓移植(BMT)的环境中，重组人IL-7增强胸腺生成的能力。我们观察到，rhIL-7治疗增强了TCD异基因骨髓移植受者的胸腺功能，但在接受即使是中等剂量的T细胞的动物中却没有，这可能是由于移植物抗宿主反应的胸腺毒性。因此，必须谨慎行事，因为IL-7在临床上被开发为一种用于异基因骨髓移植的免疫保护剂。这些结果表明，IL-7的使用应仅限于TCD BMT的设置，以获得最大的免疫功能益处和最小的毒性。(C)2002年，由美国血液病学会公布。
Impaired immune reconstitution has moved to the forefront of clinical problems limiting progress In allogeneic bone marrow transplantation (BMT). The Identification of therapies that can enhance immune reconstitution by increasing thymopoiesis is critical to solving this problem. Interleukin 7 (IL-7) is the most potent thymopoietic cytokine identified thus far. To study the effects of IL-7 on immune reconstitution and graft-versus-host disease (GVHD) following allogeneic BMT, we administered recombinant human IL-7 (rhIL-7) in a murine parent into an F1 model. Results showed that rhIL-7 therapy lowered the "threshold" T-cell dose required to induce both clinical signs of GVHD as well as lethal GVHD. Histologic analysis of GVHD target tissues revealed that rhIL-7 Increased the degree of Inflammation and tissue damage observed at all T-cell doses studied, but did not change the pattern of organs affected or the histologic appearance of the GVHD within target organs. In addition, we evaluated the capacity for rhIL-7 to enhance thymopoiesis In the setting of allogeneic T cell-depleted (TCD) and T-cell-replete BMT. We observed that rhIL-7 therapy enhanced thymic function In TCD allogeneic BM transplant recipients, but not In animals that received even modest doses of T cells presumably due to thymic toxicity of the graft-versus-host reaction. Thus, caution must be exercised as IL-7 is developed clinically as an immunorestorative agent for use In the setting of allogeneic BMT. These results suggest that use of IL-7 should be limited to the setting of TCD BMT to obtain the greatest benefit on Immune competence with the least toxicity. (C) 2002 by The American Society of Hematology.