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肝移植供体组织驻留淋巴细胞的器官特异性表型、功能特征描述及肝脏免疫耐受机制研究

Description of organ-specific phenotype, and functional characteristics of tissue resident lymphocytes from liver transplantation donor and research on immune tolerance mechanism of liver.

作者信息

Shi Yunpeng, Zhang Ping, Wang Guangyi, Liu Xingkai, Sun Xiaodong, Zhang Xin, Li Haijun, Qi Jun, Ding Lei, Li Ting, Zhang Ruoyan, Chen Yuguo, Zhou Jianpeng, Lv Guoyue, Tu Zhengkun

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Department of Emergency Surgery, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China.

出版信息

Oncotarget. 2018 Feb 15;9(21):15552-15565. doi: 10.18632/oncotarget.24514. eCollection 2018 Mar 20.

DOI:10.18632/oncotarget.24514
PMID:29643992
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5884647/
Abstract

AIM

Prior to transplantation, Donation after Cardiac Death (DCD) liver transplantation livers are perfused with preservation solution. Therefore, this provides an abundant source of human liver lymphocytes, as well as mesenteric lymph node and spleen for the study of lymphocyte subset diversity in the peripheral blood, lymph node, spleen and liver.

METHODS

Lymphocyte subsets were isolated and purified from peripheral blood, lymph node, spleen and liver perfusion, the phenotypic and functional analysis of the tissue resident lymphocyte were performed by flow cytometry.

RESULTS

In a direct comparison between blood, liver, lymph node and spleen cells from liver transplantation donors, the abundance of natural killer (NK) cells, CD3CD56NKT (NT) cells and CD8 T cells in intrahapatic lymphocytes (IHL) did not match what was present in peripheral blood and other peripheral lymphoid organs. The activation state of peripheral blood-derived lymphocytes was significantly different from lymph node-, spleen- and liver-derived cells. Intriguingly, NK cells, CD4 T cells, and CD8 T cells from liver perfusion display more suppressive characteristics, that is, express and produce more anti-inflammatory cytokine interleukin (IL)-10, less inflammatory cytokine interferon (INF)-γ.

CONCLUSION

Our findings imply that different tissues entail resident lymphocyte subsets with a distinct phenotype and function considering the organ is well vascularized, particularly in liver. It is better to understand the mechanism of liver immune tolerance.

摘要

目的

在心脏死亡后捐赠(DCD)肝移植前,用保存液灌注肝脏。因此,这为研究外周血、淋巴结、脾脏和肝脏中淋巴细胞亚群多样性提供了丰富的人肝淋巴细胞来源,以及肠系膜淋巴结和脾脏。

方法

从外周血、淋巴结、脾脏和肝脏灌注液中分离并纯化淋巴细胞亚群,通过流式细胞术对组织驻留淋巴细胞进行表型和功能分析。

结果

在对肝移植供体的血液、肝脏、淋巴结和脾脏细胞进行直接比较时,肝内淋巴细胞(IHL)中自然杀伤(NK)细胞、CD3CD56 NKT(NT)细胞和CD8 T细胞的丰度与外周血和其他外周淋巴器官中的情况不匹配。外周血来源的淋巴细胞的激活状态与淋巴结、脾脏和肝脏来源的细胞有显著差异。有趣的是,来自肝脏灌注液的NK细胞、CD4 T细胞和CD8 T细胞表现出更强的抑制特性,即表达和产生更多的抗炎细胞因子白细胞介素(IL)-10,更少的炎性细胞因子干扰素(INF)-γ。

结论

我们的研究结果表明,考虑到器官血管丰富,特别是在肝脏中,不同组织含有具有不同表型和功能的驻留淋巴细胞亚群。这有助于更好地理解肝脏免疫耐受的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/5884647/990c67e593a6/oncotarget-09-15552-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/5884647/4912791acc7d/oncotarget-09-15552-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/5884647/8e9384fcb306/oncotarget-09-15552-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/5884647/aedfec7ff1b8/oncotarget-09-15552-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/5884647/990c67e593a6/oncotarget-09-15552-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/5884647/4912791acc7d/oncotarget-09-15552-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/5884647/8e9384fcb306/oncotarget-09-15552-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/5884647/aedfec7ff1b8/oncotarget-09-15552-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a04/5884647/990c67e593a6/oncotarget-09-15552-g004.jpg

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