Dichotomous role of interferon-gamma in allogeneic bone marrow transplant.

Dichotomous role of interferon-gamma in allogeneic bone marrow transplant.
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DOI:
10.1016/j.bbmt.2009.07.015
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发表时间:
2009-11
影响因子:
4.3
通讯作者:
Waller, Edmund K.
Waller, Edmund K.
中科院分区:
医学2区
文献类型:
--
作者:
Lu, Ying;Waller, Edmund K.

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干扰素(IFN)-γ是一种多效性细胞因子,在先天性和获得性免疫中具有核心作用。作为一种有效的促炎和抗肿瘤细胞因子,IFN-γ通常被认为负责驱动细胞免疫应答。另一方面,越来越多的证据表明IFN-γ也具有免疫抑制活性。尽管IFN-γ是在急性GVHD过程中放大T细胞活化的关键因素之一,但在小鼠模型中已经证实IFN-γ在抑制移植物抗宿主病(GVHD)中的重要作用,急性GVHD是异基因骨髓移植(BMT)中的主要并发症和移植后死亡的原因。同时,IFN-γ促进移植物抗白血病(GVL)活性。分离GVL效应和GVHD是异基因骨髓移植治疗恶性血液病的最终目标。IFN-γ的这种自相矛盾的作用使得调节其活性成为最大化GVL同时最小化GVHD和改善BMT临床结果的有希望的策略。本文就IFN-γ对GVHD和GVL的影响及其作用机制作一综述。
Interferon (IFN)-γ is a pleiotropic cytokine with a central role in innate and adaptive immunity. As a potent pro-inflammatory and anti-tumor cytokine, IFN-γ is conventionally thought to be responsible for driving cellular immune response. On the other hand, accumulating evidence suggests that IFN-γ also has immuno-suppressive activity. An important role for IFN-γ in inhibiting graft-versus-host disease (GVHD) has been demonstrated in murine models, in spite of IFN-γ being one of the key factors amplifying T cell activation during the process of acute GVHD, the major complication and cause of post-transplant mortality in allogeneic bone marrow transplantation (BMT). At the same time, IFN-γ facilitates graft-versus-leukemia (GVL) activity. Dissociation of GVL effects from GVHD has been the ultimate goal of allogeneic BMT in the treatment of hematological malignancies. This paradoxical role of IFN-γ makes modulating its activity a promising strategy to maximize GVL while minimizing GVHD and improve clinical outcomes in BMT. In this review, the effects of IFN-γ on GVHD and GVL are discussed with consideration of the mechanism of IFN-γ action.
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