在减低强度造血干细胞移植后,宿主T细胞影响供体T细胞植入及移植物抗宿主病。

Host T cells affect donor T cell engraftment and graft-versus-host disease after reduced-intensity hematopoietic stem cell transplantation.

作者信息

Hardy Nancy M, Hakim Frances, Steinberg Seth M, Krumlauf Michael, Cvitkovic Romana, Babb Rebecca, Odom Jeanne, Fowler Daniel H, Gress Ronald E, Bishop Michael R

机构信息

Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Biol Blood Marrow Transplant. 2007 Sep;13(9):1022-30. doi: 10.1016/j.bbmt.2007.05.008. Epub 2007 Jul 16.

Abstract

Mixed chimerism in the T cell compartment (MCT) after reduced-intensity stem cell transplantation (RIST) may influence immune repopulation with alloreactive donor T cells. We examined effects of host T cell numbers on donor T cell engraftment and recovery and on acute graft-versus-host disease (aGVHD) in a relatively homogeneous patient population with respect to residual host T cells through quantified immune depletion prior to RIST and to donor T cells by setting the allograft T cell dose of 1x10(5) CD3+ cells/kg. In this setting, 2 patterns of early donor T cell engraftment could be distinguished by day +42: (1) early and complete donor chimerism in the T cell compartment (FDCT) and (2) persistent MCT. FDCT was associated with lower residual host CD8+ T cell counts prior to transplant and aGVHD. With persistent MCT, subsequent development of aGVHD could be predicted by the direction of change in T cell donor chimerism after donor lymphocyte infusion, and no aGVHD occurred until FDCT was established. MCT did not affect recovery of donor T cell counts. These observations suggest that the relative number and alloreactivity of donor and host T cells are more important than the absolute allograft T cell dose in determining donor engraftment and aGVHD after RIST.

摘要

减低强度干细胞移植(RIST)后T细胞区室混合嵌合体(MCT)可能会影响同种异体反应性供体T细胞的免疫重建。我们通过RIST前定量免疫清除以及设定同种异体移植T细胞剂量为1×10⁵ CD3⁺细胞/千克来处理供体T细胞,在一个残余宿主T细胞相对均一的患者群体中,研究宿主T细胞数量对供体T细胞植入、恢复以及急性移植物抗宿主病(aGVHD)的影响。在此情况下,在+42天时可区分出两种早期供体T细胞植入模式:(1)T细胞区室早期且完全的供体嵌合体(FDCT)和(2)持续性MCT。FDCT与移植前较低的残余宿主CD8⁺ T细胞计数及aGVHD相关。对于持续性MCT,供体淋巴细胞输注后T细胞供体嵌合体的变化方向可预测随后aGVHD的发生,且在建立FDCT之前未发生aGVHD。MCT不影响供体T细胞计数的恢复。这些观察结果表明,在确定RIST后供体植入和aGVHD方面,供体和宿主T细胞的相对数量及同种异体反应性比绝对的同种异体移植T细胞剂量更为重要。

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