Prevention of graft-versus-host disease by anti-1L-7Rα antibody
Prevention of graft-versus-host disease by anti-1L-7Rα antibody
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DOI：
10.1182/blood-2006-11-055673
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发表时间：
2007-10-15
期刊：
影响因子：
20.3
通讯作者：
Weinberg, Kenneth I.
中科院分区：
文献类型：
--
作者：
Chung, Brile;Dudl, Eric P.;Weinberg, Kenneth I.
移植物抗宿主病（GVHD）仍然是限制异基因骨髓移植（BMT）成功的严重并发症。使用IL-7缺陷的小鼠模型，我们以前已经表明，IL-7是必要的GVHD的发病机制。在本研究中，我们确定了GVHD是否可以通过抗体介导的IL-7受体α（IL-7 R α）信号转导阻断来预防。对C57/BL 6（H2K（B））受体小鼠进行致死性照射，并与同种异体BALB/c（H2K（d））供体小鼠的T细胞去除（TCD）ISM和淋巴结（LN）细胞进行共移植。移植后，每周用抗IL-7 R α抗体（每周每只小鼠100 μ g）或PBS注射同种异体BMT受体4周。抗IL-7 R α。与安慰剂相比，抗体治疗显著降低了GVHD相关的发病率和死亡率（30%至80%）。IL-7 R α阻断导致移植后第30天外周中供体CD 4（+）或CD 8（+）T细胞减少。特别地，通过抗IL-7 R α抗体治疗抑制GVHD导致改善的长期胸腺和免疫功能。通过抗IL-7 R α抗体阻断IL-7 R导致同种异体反应性T细胞的消除、GVHD的预防和供体T细胞重建的改善。
Graft-versus-host disease (GVHD) continues to be a serious complication that limits the success of allogeneic bone marrow transplantation (BMT). Using IL-7-deficient murine models, we have previously shown that IL-7 is necessary for the pathogenesis of GVHD. In the present study, we determined whether GVHD could be prevented by anti body-mediated blockade of IL-7 receptor alpha (IL-7R alpha) signaling. C57/BL6 (H2K(b)) recipient mice were lethally irradiated and underwent cotransplantation with T-cell-depleted (TCD) ISM and lymph node (LN) cells from allogeneic BALB/c (H2K(d)) donor mice. Following transplantation, the allogeneic BMT recipients were injected weekly with either anti-IL-7R alpha antibody (100 mu g per mouse per week) or PBS for 4 weeks. Anti-IL-7R alpha. antibody treatment significantly decreased GVHD-related morbidity and mortality compared with placebo (30% to 80%). IL-7R alpha blockade resulted in the reduction of donor CD4(+) or CD8(+) T cells in the periphery by day 30 after transplantation. Paradoxically, the inhibition of GVHD by anti-IL-7R alpha antibody treatment resulted in improved long-term thymic and immune function. Blockade of IL-7R by anti-IL-7R alpha antibody resulted in elimination of alloreactive T cells, prevention of GVHD, and improvement of donor T-cell reconstitution.