Common lymphoid progenitors rapidly engraft and protect against lethal murine cytomegalovirus infection after hematopoietic stem cell transplantation
Common lymphoid progenitors rapidly engraft and protect against lethal murine cytomegalovirus infection after hematopoietic stem cell transplantation
复制标题
DOI：
10.1182/blood-2002-12-3834
复制
发表时间：
2003-07-15
期刊：
影响因子：
20.3
通讯作者：
Brown, JMY
中科院分区：
文献类型：
--
作者：
Arber, C;BitMansour, A;Brown, JMY
异基因造血细胞移植(HCT)后淋巴系缺陷会增加感染的易感性；然而，成熟淋巴细胞移植经常会导致一种称为移植物抗宿主病(GVHD)的严重并发症。在这里，我们在小鼠身上证明了低数量高纯度的共同淋巴祖细胞(CLP)的同种和同种异体移植--一种罕见的致力于淋巴系的骨髓细胞--在致死照射和造血干细胞(HSCs)挽救后加速免疫重建。同种移植后，3×10(3)UPS对小鼠巨细胞病毒(MCMV)感染的保护作用大致相当于10(7)个完整的淋巴结细胞。在匹配的非亲缘供者HSC移植的同种异体模型中，3×10(3)个CLP的联合移植可以保护胸腺和切除胸腺的宿主免受MCMV感染和减轻疾病严重程度。免疫组织化学结合T细胞和自然杀伤(NK)细胞的抗体去除证实了CLP来源的淋巴细胞和残留的宿主淋巴细胞有助于抗病毒保护。重要的是，同种异体CLP移植提供了持久的抗病毒免疫，而不会导致GVHD。这些数据支持用承诺的祖细胞组成移植物以降低HCT后对病毒感染的易感性的可能性。(C)2003年，由美国血液病学会提供。
Lymphoid deficiency after allogeneic hematopoietic cell transplantation (HCT) results in increased susceptibility to infection; however, transplantation of mature lymphocytes frequently results in a serious complication known as graft-versus-host disease (GVHD). Here we demonstrate in mice that both congenic as well as allogeneic transplantation of low numbers of highly purified common lymphoid progenitors (CLPs)-a rare population of lymphoid-lineage-committed bone marrow cells-accelerates immune reconstitution after lethal irradiation and rescue with hematopoietic stem cells (HSCs). After congenic transplantation, 3 x 10(3) Ups protected against murine cytomegalovirus (MCMV) infection at a level roughly equivalent to 10(7) unfractionated lymph node cells. In the allogeneic model of matched unrelated donor HSC transplantation, cotransplantation of 3 x 10(3) CLPs protected thymus-bearing as well as thymectomized hosts from MCMV infection and attenuated disease severity. Immunohistochemistry in combination with antibody depletion of T and natural killer (NK) cells confirmed that CLP-derived as well as residual host lymphocytes contribute to antiviral protection. Importantly, transplantation of allogeneic CLPs provided a durable antiviral immunity without inducing GVHD. These data support the potential for composing grafts with committed progenitors to reduce susceptibility to viral infection following HCT. (C) 2003 by The American Society of Hematology.