Allogeneic splenocyte transfer and lipopolysaccharide inhalations induce differential T cell expansion and lung injury: a novel model of pulmonary graft-versus-host disease.
Allogeneic splenocyte transfer and lipopolysaccharide inhalations induce differential T cell expansion and lung injury: a novel model of pulmonary graft-versus-host disease.
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DOI：
10.1371/journal.pone.0097951
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Palmer SM
中科院分区：
文献类型：
--
作者：
Martinu T;Kinnier CV;Sun J;Kelly FL;Nelson ME;Garantziotis S;Foster WM;Palmer SM
肺部 GVHD (pGVHD) 是造血细胞移植 (HCT) 的重要并发症，被认为是 HCT 预处理方案、同种异体供体细胞和移植后肺部暴露的结果。我们之前已经证明，连续吸入脂多糖（LPS）暴露会增强小鼠同种异体 HCT 后 pGVHD 的发生。在当前的研究中，我们假设在没有预处理方案的情况下，仅同种异体淋巴细胞和环境暴露就会导致 pGVHD 的特征，并导致与同系细胞相比不同的 T 细胞扩增模式。受体 Rag1−/− 小鼠接受同种异体 (Allo) 或同基因 (Syn) 脾细胞的移植。免疫重建1周后，小鼠每天接受5次吸入LPS暴露，并在最后一次LPS暴露后72小时处死。评估了肺生理学、组织学和支气管肺泡灌洗液 (BAL) 中的蛋白质水平。通过流式细胞术分析肺细胞。接受 LPS 暴露的 Allo 和 Syn 小鼠（AlloLPS 和 SynLPS）的肺部都有明显的淋巴细胞炎症，类似于 pGVHD 病理，这在未暴露 LPS 或未移植的对照中未见。然而，与 SynLPS 相比，AlloLPS 显着增加了 BAL 蛋白水平并增强了气道高反应性，这与更严重的肺损伤一致。 AlloLPS 小鼠中的这种损伤与 CD8 T 细胞和效应 CD4 T 细胞的增加以及调节性与效应 CD4 T 细胞比率的降低有关。此外，细胞因子分析与优先 Th1 分化以及肺 CCL5 和颗粒酶 B 的上调一致。同种异体淋巴细胞转移到淋巴细胞缺陷小鼠中，然后暴露于 LPS，在没有预处理 HCT 方案的情况下会导致 pGVHD 和肺损伤的特征。这种与同种异体效应 T 细胞扩增相关的肺部疾病提供了一种新模型来剖析独立于调节的 pGVHD 机制。
Pulmonary GVHD (pGVHD) is an important complication of hematopoietic cell transplant (HCT) and is thought to be a consequence of the HCT conditioning regimen, allogeneic donor cells, and posttransplant lung exposures. We have previously demonstrated that serial inhaled lipopolysaccharide (LPS) exposures potentiate the development of pGVHD after murine allogeneic HCT. In the current study we hypothesized that allogeneic lymphocytes and environmental exposures alone, in the absence of a pre-conditioning regimen, would cause features of pGVHD and would lead to a different T cell expansion pattern compared to syngeneic cells. Recipient Rag1−/− mice received a transfer of allogeneic (Allo) or syngeneic (Syn) spleen cells. After 1 week of immune reconstitution, mice received 5 daily inhaled LPS exposures and were sacrificed 72 hours after the last LPS exposure. Lung physiology, histology, and protein levels in bronchoalveolar lavage (BAL) were assessed. Lung cells were analyzed by flow cytometry. Both Allo and Syn mice that undergo LPS exposures (AlloLPS and SynLPS) have prominent lymphocytic inflammation in their lungs, resembling pGVHD pathology, not seen in LPS-unexposed or non-transplanted controls. Compared to SynLPS, however, AlloLPS have significantly increased levels of BAL protein and enhancement of airway hyperreactivity, consistent with more severe lung injury. This injury in AlloLPS mice is associated with an increase in CD8 T cells and effector CD4 T cells, as well as a decrease in regulatory to effector CD4 T cell ratio. Additionally, cytokine analysis is consistent with a preferential Th1 differentiation and upregulation of pulmonary CCL5 and granzyme B. Allogeneic lymphocyte transfer into lymphocyte-deficient mice, followed by LPS exposures, causes features of pGVHD and lung injury in the absence of a pre-conditioning HCT regimen. This lung disease associated with an expansion of allogeneic effector T cells provides a novel model to dissect mechanisms of pGVHD independent of conditioning.
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影响因子：
3.8
作者：
Brandon, J. Anthony;Jennings, C. Darrell;Kaplan, Alan M.;Bryson, J. Scott
通讯作者：
Bryson, J. Scott
影响因子：
6.2
作者：
Garantziotis, Stavros;Palmer, Scott M.;Schwartz, David A.
通讯作者：
Schwartz, David A.
影响因子：
4.4
作者：
Koya, Toshiyuki;Miyahara, Nobuaki;Gelfand, Erwin W.
通讯作者：
Gelfand, Erwin W.
影响因子：
4.4
作者：
Miyahara, N;Takeda, K;Gelfand, EW
通讯作者：
Gelfand, EW
影响因子：
6.1
作者：
MICHEL, O;GINANNI, R;SERGYSELS, R
通讯作者：
SERGYSELS, R