Virotherapy using myxoma virus prevents lethal graft-versus-host disease following xeno-transplantation with primary human hematopoietic stem cells.

Virotherapy using myxoma virus prevents lethal graft-versus-host disease following xeno-transplantation with primary human hematopoietic stem cells.
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DOI:
10.1371/journal.pone.0043298
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
McFadden G
McFadden G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bartee E;Meacham A;Wise E;Cogle CR;McFadden G

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移植物抗宿主病(GVHD)是一种潜在的致死性临床并发症,由同种异体反应性T淋巴细胞转移到免疫功能低下的受体中引起。尽管传统的T细胞耗尽方法,GVHD仍然是同种异体造血细胞移植的主要挑战。在这里,我们展示了一种新的方法,通过用黏液瘤病毒体外治疗原代人造血细胞源来预防GVHD。黏液瘤病毒是一种兔特异性痘病毒,目前正在开发用于溶瘤病毒治疗。这种预处理可显著提高原代人骨髓或外周血注射免疫功能低下小鼠的移植后存活率,并可阻止人CD3+淋巴细胞在主要受体器官中的扩增。类似的病毒治疗也能在体外阻止人-人混合同种异体反应性T淋巴细胞反应。我们的数据表明,用黏液瘤病毒进行体外病毒治疗可以是一种简单有效的方法来预防GVHD后输注含有同种异体T淋巴细胞的造血产品,如:同种异体造血干细胞和祖细胞,供体白细胞输注和输血。
Graft-versus-host disease (GVHD) is a potentially lethal clinical complication arising from the transfer of alloreactive T lymphocytes into immunocompromised recipients. Despite conventional methods of T cell depletion, GVHD remains a major challenge in allogeneic hematopoietic cell transplant. Here, we demonstrate a novel method of preventing GVHD by ex vivo treatment of primary human hematopoietic cell sources with myxoma virus, a rabbit specific poxvirus currently under development for oncolytic virotherapy. This pretreatment dramatically increases post-transplant survival of immunocompromised mice injected with primary human bone marrow or peripheral blood cells and prevents the expansion of human CD3+ lymphocytes in major recipient organs. Similar viral treatment also prevents human-human mixed alloreactive T lymphocyte reactions in vitro. Our data suggest that ex vivo virotherapy with myxoma virus can be a simple and effective method for preventing GVHD following infusion of hematopoietic products containing alloreactive T lymphocytes such as: allogeneic hematopoietic stem and progenitor cells, donor leukocyte infusions and blood transfusions.
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