Recombinant IL-7/HGFβ hybrid cytokine enhances T cell recovery in mice following allogeneic bone marrow transplantation.
Recombinant IL-7/HGFβ hybrid cytokine enhances T cell recovery in mice following allogeneic bone marrow transplantation.
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DOI：
10.1371/journal.pone.0082998
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rood D
中科院分区：
文献类型：
--
作者：
Lai L;Zhang M;Song Y;Rood D
T细胞免疫缺陷是骨髓移植的主要并发症。因此，需要增强BMT后T细胞重建的方法。我们从一个独特的长期骨髓培养系统中纯化了一种由IL-7和肝细胞生长因子β（HGFβ）β链组成的混合细胞因子（IL-7/HGFβ）。我们克隆并表达了IL-7/HGFβ基因，其中IL-7和HGFβ基因通过柔性接头连接，以产生rIL-7/HGFβ蛋白。在这里，我们发现rIL-7/HGFβ处理增强了异基因BMT后的胸腺生成。尽管rIL-7处理也能增加胸腺细胞的数量，但rIL-7/HGFβ杂合细胞因子比rIL-7更有效，而且rIL-7和rIL-7/HGFβ增加胸腺细胞数量的机制不同。rIL-7增强双阴性（DN）、CD 4和CD 8单阳性（SP）胸腺细胞的存活。相反，rIL-7/HGFβ促进DN、SP胸腺细胞的增殖，以及CD 4和CD 8双阳性（DP）胸腺细胞的存活。rIL-7/HGFβ处理还增加早期胸腺祖细胞（ETP）和胸腺上皮细胞（TEC）的数量。rIL-7/HGFβ处理的异基因骨髓移植受者胸腺重建增强，导致外周血T细胞数量和功能活性增加。rIL-7/HGFβ处理的BMT小鼠未诱发移植物抗宿主病（GVHD）。因此，rIL-7/HGFβ可能为BMT后T细胞免疫缺陷的预防和/或治疗提供新的工具。
T cell immunodeficiency is a major complication of bone marrow (BM) transplantation (BMT). Therefore, approaches to enhance T cell reconstitution after BMT are required. We have purified a hybrid cytokine, consisting of IL-7 and the β-chain of hepatocyte growth factor (HGFβ) (IL-7/HGFβ), from a unique long-term BM culture system. We have cloned and expressed the IL-7/HGFβ gene in which the IL-7 and HGFβ genes are connected by a flexible linker to generate rIL-7/HGFβ protein. Here, we show that rIL-7/HGFβ treatment enhances thymopoiesis after allogeneic BMT. Although rIL-7 treatment also enhances the number of thymocytes, rIL-7/HGFβ hybrid cytokine was more effective than was rIL-7 and the mechanisms by which rIL-7 and rIL-7/HGFβ increase the numbers of thymocytes are different. rIL-7 enhances the survival of double negative (DN), CD4 and CD8 single positive (SP) thymocytes. In contrast, rIL-7/HGFβ enhances the proliferation of the DN, SP thymocytes, as well as the survival of CD4 and CD8 double positive (DP) thymocytes. rIL-7/HGFβ treatment also increases the numbers of early thymocyte progenitors (ETPs) and thymic epithelial cells (TECs). The enhanced thymic reconstitution in the rIL-7/HGFβ-treated allogeneic BMT recipients results in increased number and functional activities of peripheral T cells. Graft-versus-host-disease (GVHD) is not induced in the rIL-7/HGFβ-treated BMT mice. Therefore, rIL-7/HGFβ may offer a new tool for the prevention and/or treatment of T cell immunodeficiency following BMT.
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影响因子：
15.9
作者：
Lai, Laijun;Zhang, Mingfeng;Goldschneider, Irving
通讯作者：
Goldschneider, Irving
影响因子：
64.8
作者：
MOMBAERTS, P;CLARKE, AR;TONEGAWA, S
通讯作者：
TONEGAWA, S
影响因子：
20.3
作者：
Lai, Laijun;Cui, Cheng;Zhao, Yong
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Zhao, Yong
影响因子：
20.3
作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
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