Host reactive donor T cells are associated with lung injury after experimental allogeneic bone marrow transplantation
Host reactive donor T cells are associated with lung injury after experimental allogeneic bone marrow transplantation
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DOI：
10.1182/blood.v92.7.2571.2571_2571_2580
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发表时间：
1998-10-01
期刊：
影响因子：
20.3
通讯作者：
Ferrara, JLM
中科院分区：
文献类型：
--
作者：
Cooke, KR;Krenger, W;Ferrara, JLM
非感染性肺损伤是异基因骨髓移植（BMT）后常见的并发症，但其与急性移植物抗宿主病（GVHD）的关系尚不清楚。本研究利用小鼠BMT系统（供者和宿主存在多种次要组织相容性（H）抗原差异），研究了肺损伤的性质及其与系统性GVHD和宿主反应性供者T细胞的关系。致死性辐照CBA宿主接受同基因BMT或同种异体（B10.BR）T细胞去除（TCD）骨髓（BM），添加或不添加T细胞。BMT后6周，与同基因对照组相比，在接受同种异体BMT的动物中观察到显著的肺组织病理学变化。接受同种异体T细胞并发生GVHD的小鼠的肺损伤更大，但在TCD BMT后，当临床和组织学急性GVHD体征不存在时，也可检测到肺损伤。在每种情况下，肺损伤与肺功能的显著改变相关。与同基因对照组相比，在所有同种异体BMT接受者的支气管肺泡灌洗液（BAL）中，成熟的供体（V β 6（+）和V β 3（+））T细胞显著增加，这些细胞在体外增殖并产生针对宿主抗原的干扰素-γ（IFN-γ）。这些体外反应与BAL液中IFN-γ和肿瘤坏死因子-α（TNF-α）升高相关。我们的结论是，同种异体供者淋巴细胞与肺损伤在这个异基因骨髓移植模型。这些细胞在BAL液中的扩增及其对宿主抗原的反应能力，即使在建立了全身耐受性（即，不存在临床GVHD）的情况下，也表明肺可作为这些宿主反应性供体T细胞的避难所。这些发现可能具有重要意义的评估和治疗肺功能障碍后同种异体骨髓移植，即使临床GVHD是缺席。(C)1998年美国血液学会。
Noninfectious lung injury is common after allogeneic bone marrow transplantation (BMT), but its association with acute graft-versus-host disease (GVHD) is unclear, Using a murine BMT system where donor and host differ by multiple minor histocompatibility (H) antigens, we investigated the nature of lung injury and its relationship both to systemic GVHD and host-reactive donor T cells. Lethally irradiated CBA hosts received syngeneic BMT or allogeneic (B10.BR) T-cell-depleted (TCD) bone marrow (BM) with and without the addition of T cells. Six weeks after BMT, significant pulmonary histopathology was observed in animals receiving allogeneic BMT compared with syngeneic controls. Lung damage was greater in mice that received allogeneic T cells and developed GVHD, but it was also detectable after TCD BMT when signs of clinical and histologic acute GVHD were absent. In each setting, lung injury was associated with significant alterations in pulmonary function. Mature, donor (V beta 6(+) and V beta 3(+))T cells were significantly increased in the broncho-alveolar lavage (BAL) fluid of all allogeneic BMT recipients compared with syngeneic controls, and these cells proliferated and produced interferon-gamma (IFN-gamma) to host antigens in vitro. These in vitro responses correlated with increased IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in the BAL fluid. We conclude that alloreactive donor lymphocytes are associated with lung injury in this allogeneic BMT model. The expansion of these cells in the BAL fluid and their ability to respond to host antigens even when systemic tolerance has been established (ie, the absence of clinical GVHD) suggest that the lung may serve as a sanctuary site for these host reactive donor T cells. These findings may have important implications with regard to the evaluation and treatment of pulmonary dysfunction after allogeneic BMT even when clinical GVHD is absent. (C) 1998 by The American Society of Hematology.