Zhang Yi, Joe Gerard, Hexner Elizabeth, Zhu Jiang, Emerson Stephen G
Department of Medicine, University of Pennsylvania School of Medicine, Room 510, Maloney, 3600 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
Nat Med. 2005 Dec;11(12):1299-305. doi: 10.1038/nm1326. Epub 2005 Nov 20.
Graft-versus-host disease (GVHD) is caused by alloreactive donor T cells that trigger host tissue injury. GVHD develops over weeks or months, but how this immune response is maintained over time is unknown. In mouse models of human GVHD, we identify a new subset of postmitotic CD44(lo)CD62L(hi)CD8(+) T cells that generate and sustain all allogeneic T-cell subsets in GVHD reactions, including central memory, effector memory and effector CD8(+) T cells, while self-renewing. These cells express Sca-1, CD122 and Bcl-2, and induce GVHD upon transfer into secondary recipients. The postmitotic CD44(lo)CD62L(hi)CD8(+) T cells persist throughout the course of GVHD, are generated in the initial phase in response to alloantigens and dendritic cells and require interleukin-15. Thus, their long life, ability to self-renew and multipotentiality define these cells as candidate memory stem cells. Memory stem cells will be important targets for understanding and influencing diverse chronic immune reactions, including GVHD.
移植物抗宿主病（GVHD）由引发宿主组织损伤的同种异体反应性供体T细胞引起。GVHD在数周或数月内发展，但这种免疫反应如何随时间维持尚不清楚。在人类GVHD的小鼠模型中，我们鉴定出有丝分裂后CD44(lo)CD62L(hi)CD8(+) T细胞的一个新亚群，该亚群在GVHD反应中产生并维持所有同种异体T细胞亚群，包括中枢记忆T细胞、效应记忆T细胞和效应CD8(+) T细胞，同时进行自我更新。这些细胞表达Sca-1、CD122和Bcl-2，并在转移至二级受体后诱导GVHD。有丝分裂后CD44(lo)CD62L(hi)CD8(+) T细胞在GVHD病程中持续存在，在初始阶段因同种异体抗原和树突状细胞而产生，并且需要白细胞介素-15。因此，它们的长寿命、自我更新能力和多能性将这些细胞定义为候选记忆干细胞。记忆干细胞将成为理解和影响包括GVHD在内的各种慢性免疫反应的重要靶点。
