In vivo analyses of early events in acute graft-versus-host disease reveal sequential infiltration of T-cell subsets
In vivo analyses of early events in acute graft-versus-host disease reveal sequential infiltration of T-cell subsets
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DOI：
10.1182/blood-2005-02-0509
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发表时间：
2005-08-01
期刊：
影响因子：
20.3
通讯作者：
Negrin, RS
中科院分区：
文献类型：
--
作者：
Beilhack, A;Schulz, S;Negrin, RS
移植物抗宿主病(GVHD)是异基因造血细胞移植的主要障碍。鉴于GVHD中免疫细胞亚群和组织结构的动态变化，体内关键免疫事件的定位和时间可能揭示GVHD的基本发病机制。为此，我们移植了荧光素酶标记的同种异体脾细胞，并通过体内生物柱状成像监测组织分布。高分辨率分析显示，捐赠者的CD4(+)T细胞最初增殖，随后CD8(+)T细胞在次级淋巴器官中增殖，随后归巢到肠、肝脏和皮肤。纯化的幼稚T细胞移植引起GVHD，首先发生在次级淋巴器官，然后是肠道、肝脏和皮肤的靶器官表现。相反，移植的CD4+效应记忆T(T-EM)细胞在体内次级淋巴器官中不增殖，尽管它们在体外混合白细胞反应(MLFI)检测中具有同种异体反应，但并未导致急性GVHD。这些发现强调了具有明确运输模式的T细胞亚群在没有移植物抗宿主病风险的情况下用于免疫重建的潜力。
Graft-versus-host disease (GVHD) is a major obstacle in allogeneic hematopoietic cell transplantation. Given the dynamic changes in immune cell subsets and tissue organization, which occur in GVHD, localization and timing of critical immunological events in vivo may reveal basic pathogenic mechanisms. To this end, we transplanted luciferase-labeled allogeneic splenocytes and monitored tissue distribution by in vivo biolumines-cence imaging. High-resolution analyses showed initial proliferation of donor CD4(+) T cells followed by CD8(+) T cells in secondary lymphold organs with subsequent homing to the intestines, liver, and skin. Transplantation of purified naive T cells caused GVHD that was initiated In secondary lymphoid organs followed by target organ manifestation In gut, liver, and skin. In contrast, transplanted CD4+ effector memory T (T-EM) cells did not proliferate In secondary lymphold organs in vivo and despite their in vitro alloreactivity in mixed leukocyte reaction (MLFI) assays did not cause acute GVHD. These findings underline the potential of T-cell subsets with defined trafficking patterns for immune reconstitution without the risk of GVHD.