Amelioration of graft versus host disease by galectin-1
Amelioration of graft versus host disease by galectin-1
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DOI：
10.1016/j.clim.2003.08.003
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发表时间：
2003-12-01
影响因子：
8.6
通讯作者：
Baldwin, GC
中科院分区：
文献类型：
--
作者：
Baum, LG;Blackall, DP;Baldwin, GC
移植物抗宿主病是异基因造血干细胞移植后发病和死亡的重要原因。半乳糖凝集素-1是一种调节T细胞功能和细胞凋亡的哺乳动物凝集素，在自身免疫性疾病的动物模型中显示出免疫调节作用。我们研究了半乳糖凝集素-1在移植物抗宿主病小鼠模型中的疗效，发现68%的半乳糖凝集素-1治疗小鼠存活，而溶媒治疗小鼠存活率为3%。半乳糖凝集素-I处理的动物与仅用媒介物处理的动物相比，组织中的炎性浸润也减少。Galectim-1不影响供体造血细胞的植入。然而，与仅用溶媒处理的动物相比，半乳糖凝集素-1处理的动物显示骨髓和脾脏中细胞结构增加，脾B细胞和CD 4 T细胞数量增加。半乳糖凝集素-1治疗还显著改善了移植后正常脾结构的重建。与单独使用溶剂处理的动物相比，半乳凝素-I处理的移植小鼠的脾细胞中I型细胞因子白细胞介素-2（IL-2）和干扰素-γ的产生减少，而II型细胞因子IL-4和IL-10的产生在两组动物之间相似。虽然半乳糖凝集素-I治疗的移植动物的脾细胞对第三方抗原和白血病攻击都有反应，但与溶媒治疗动物的细胞相比，宿主同种异体反应性显著降低。这些结果表明，半乳糖凝集素-1疗法能够增加存活率并抑制移植物抗宿主免疫应答，而不损害同种异体造血干细胞移植后的植入或免疫重建。(C)2003年爱思唯尔公司All rights reserved.
Graft versus host disease is a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Galectin-1, a mammalian lectin that modulates T cell function and apoptosis, has been shown to be immunomodulatory in animal models of autoimmune disease. We investigated the efficacy of galectin-1 in a murine model of graft versus host disease and found that 68% of galectin-1-treated mice survived, compared to 3% of vehicle-treated mice. Galectin-I-treated animals also had reduced inflammatory infiltrates in tissues compared to animals treated with vehicle alone. Galectim-1 did not affect engraftment of donor hematopoietic cells. However, galectin-1-treated animals demonstrated increased cellularity in bone marrow and spleen with increased numbers of splenic B cells and CD4 T cells compared to those animals treated with vehicle alone. Galectin-1 treatment also significantly improved reconstitution of normal splenic architecture following transplant. Production of type I cytokines interleukin-2 (IL-2) and interferon-gamma was reduced in splenocytes derived from galectin-I-treated transplanted mice when compared to animals treated with vehicle alone, while production of the type II cytokines, IL-4 and IL-10, was similar between the two groups of animals. Although splenocytes from galectin-I-treated transplanted animals responded to both third party antigens and leukemic challenge, host alloreactivity was significantly reduced when compared to cells from vehicle-treated animals. These results demonstrate that galectin-1 therapy is capable of increasing survival and suppressing the graft versus host immune response without compromising engraftment or immune reconstitution following allogeneic hematopoietic stem cell transplant. (C) 2003 Elsevier Inc. All rights reserved.