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[浸润性CD3 T细胞的动力学及其与移植物抗宿主病靶器官损伤的关系]

[Kinetics of Infiltrating CD3 T Cells and Their Relationship with Target Organ Injury of Graft-Versus-Host Disease].

作者信息

Zhao Kai, Ruan Su-Hong, Tian Yu, Xu Kai-Lin

机构信息

Blood Diseases Institute, Xuzhou Medical University, Department of Hematology of The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China.

Blood Diseases Institute, Xuzhou Medical University, Department of Hematology of The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China,Department of Hematology, Suzhou Municipal Hospital, Suzhou 215002, Jiangsu Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021 Jun;29(3):931-936. doi: 10.19746/j.cnki.issn.1009-2137.2021.03.044.

Abstract

OBJECTIVE

To explore the kinetics of infiltrated T cell in murine acute graft-versus-host disease (aGVHD) target organs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its relationship with tissue pathological damage and aGVHD progress.

METHODS

Male C57BL/6 (H-2K) mice at age of 8-10 weeks were selected as donors, from which splenic cells and bone marrow cells were isolated. And 10-12 weeks of BALB/c (H-2K) male mice which received 7.5 Gy total body irradiation (TBI) were recipients to transplant. Recipients were randomly divided into allogeneic bone marrow transplantation (BMT) group and BMT+T group, which were transplanted bone marrow cells with or without splenic cells, respectively. All recipients were daily monitored and the dynamic changes of the body weights along with clinical scores of aGVHD were detected. HE staining was used to investigate the pathological damage and score of aGVHD target organs. The number of infiltrated CD3 T cells in target organs was numerated and statistically analyzed after immunohistochemistry staining on day 7, 14, 28, 40 and 47 after transplantation.

RESULTS

Compared with BMT group, the number of infiltrated T cells in aGVHD target organs including liver, lung and gut increased since day 7 in BMT+T group (P<0.05). On day 14, 28, 40 and 47 after transplantation, more infiltrated CD3 T cells were detected in target tissues of mice in BMT+T group than those in BMT group (P<0.05). Higher clinical score and histopathological score of target organs in aGVHD mice were detected (P<0.05). Positive correlation was found in the number of liver infiltrated T cells and pathological damage, and the numbers of infiltrated CD3 T cells in gut were positively related to aGVHD clinical scores.

CONCLUSION

Pathological damage of aGVHD target organs is induced by CD3 T cell infiltration, and the number of infiltrated T cell may be an important evaluated index of aGVHD severity.

摘要

目的

探讨异基因造血干细胞移植(allo-HSCT)后小鼠急性移植物抗宿主病(aGVHD)靶器官中浸润T细胞的动力学变化及其与组织病理损伤和aGVHD进展的关系。

方法

选取8-10周龄雄性C57BL/6(H-2K)小鼠作为供体,分离其脾细胞和骨髓细胞。选取10-12周龄接受7.5 Gy全身照射(TBI)的BALB/c(H-2K)雄性小鼠作为受体进行移植。受体随机分为异基因骨髓移植(BMT)组和BMT+T组,分别移植有或无脾细胞的骨髓细胞。每日监测所有受体,检测体重动态变化及aGVHD临床评分。采用HE染色观察aGVHD靶器官的病理损伤并评分。移植后第7、14、28、40和47天进行免疫组化染色后计数并统计分析靶器官中浸润CD3 T细胞的数量。

结果

与BMT组相比,BMT+T组自第7天起,aGVHD靶器官(包括肝、肺和肠道)中浸润T细胞数量增加(P<0.05)。移植后第14、28、40和47天,BMT+T组小鼠靶组织中检测到的浸润CD3 T细胞比BMT组更多(P<0.05)。检测到aGVHD小鼠靶器官的临床评分和组织病理学评分更高(P<0.05)。肝浸润T细胞数量与病理损伤呈正相关,肠道浸润CD3 T细胞数量与aGVHD临床评分呈正相关。

结论

CD3 T细胞浸润诱导aGVHD靶器官的病理损伤,浸润T细胞数量可能是评估aGVHD严重程度的重要指标。

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