The pathophysiology of chronic graft-versus-host disease
The pathophysiology of chronic graft-versus-host disease
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DOI：
10.1532/ijh97.04015
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发表时间：
2004-04-01
影响因子：
2.1
通讯作者：
Kansu, E
中科院分区：
文献类型：
--
作者：
Kansu, E
慢性移植物抗宿主病（GVHD）仍然是异基因造血干细胞移植后最重要的并发症。这种疾病通常出现在第100天之后，其特征是类似于自身免疫性疾病的体征和症状。慢性GVHD的病理生理学是知之甚少，因为缺乏高度满意的动物模型和患者的基础研究。目前还没有明确确定这种疾病是一种独特的实体还是急性GVHD的延续。在慢性GVHD的实验和临床研究中，已经描述了胸腺萎缩、淋巴细胞耗竭和自身抗体形成。预处理方案和急性GVHD可能会破坏胸腺功能和失调的潜在自身反应性T淋巴细胞的负选择过程。胸腺细胞凋亡的破坏和不能清除大部分自身反应性淋巴细胞可能导致淋巴细胞稳态和自身耐受的损害。自身反应性T细胞的扩增和效应子功能随后将促进自身反应性B细胞活化和产生具有靶器官损伤的自身抗体。慢性GVHD需要持续的CD 4（+）T细胞帮助B细胞，被称为辅助性T细胞2（Th 2）疾病。小鼠模型已经证实了白细胞介素（IL）-12和IL-18在慢性GVHD中的作用。IL-12可能导致供体CD 8（+）细胞毒性T细胞增加，导致慢性GVHD转化为急性形式。相比之下，IL-18通过减少CD 4（+）（Th 2）细胞和宿主反应性B细胞活化的数量以及减少同种异体抗原特异性免疫应答来预防慢性GVHD。小鼠和人类细胞基因组学加上细胞生物学在供体-受体耐受性方面的进展将提高我们对移植免疫学的理解，并可能为改善慢性GVHD的挑战提供新的方法。(C)2004年日本血液学会。
Chronic graft-versus-host disease (GVHD) still remains the most significant complication after allogeneic hematopoietic stem cell transplantation. The disease usually appears after day 100 and is characterized by signs and symptoms similar to autoimmune diseases. The pathophysiology of chronic GVHD is poorly understood because of the lack of highly satisfactory animal models and basic studies in patients. It has not been clearly determined whether the disease is a distinct entity or a continuation of acute GVHD. In experimental and clinical studies of chronic GVHD, thymic atrophy, lymphocyte depletion, and autoantibody formation have been described. Conditioning regimens and acute GVHD may disrupt thymic function and dysregulate the negative selection process of potentially autoreactive T-lymphocytes. Disruption of thymic apoptosis and failure to eliminate the majority of self-reactive lymphocytes may lead to impairment of lymphocyte homeostasis and self tolerance. Expansion and effector functions of autoreactive T-cells will then promote autoreactive B-cell activation and production of autoantibodies with target-organ damage. Chronic GVHD requires continuous CD4(+) T-cell help for B-cells and is known as T-helper 2 (Th2) disease. Murine models have demonstrated the roles of interleukin (IL)-12 and IL-18 in chronic GVHD. IL-12 may cause an increase in donor CD8(+) cytotoxic T-cells leading to conversion of chronic GVHD to an acute form. In contrast, IL-18 prevents chronic GVHD by decreasing numbers of CD4(+) (Th2) cells and host-reactive B-cell activation and reducing alloantigen-specific immune response. Mouse and human cellular genomics coupled with advances in cell biology in donor-recipient tolerance will improve our understanding of transplantation immunology and may offer new approaches to the challenge of ameliorating chronic GVHD. (C) 2004 The Japanese Society of Hematology.