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不同免疫抑制治疗下肾移植受者外周免疫细胞的特征分析

Characterization of peripheral immune cells in kidney transplantation recipients under different immunosuppressive treatments.

作者信息

Tai Yunze, Li Nanjing, Fan Jiwen, Zhang Haohan, Long Honghui, Yan Lin, Feng Weihua, Zhang Junlong, Cai Bei, Fan Yu, Luo Yao, Li Yi

机构信息

Department of Laboratory Medicine, Sichuan Medical Laboratory Clinical Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Division of Radiotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Front Immunol. 2025 Jun 11;16:1605664. doi: 10.3389/fimmu.2025.1605664. eCollection 2025.

Abstract

BACKGROUND

A comprehensive peripheral immune cell characterization including novel immunosuppressive subsets myeloid-derived suppressive cells (MDSCs) in kidney transplant recipients (KTRs) under different immunosuppressive treatments can help: 1) Immunosuppression situation and allograft acceptance assessment; 2) Infection and rejection emergence indication; 3) Beneficial immunosuppressive regimens' selection.

METHODS

26 KTRs with an average transplant duration of 360 days and 13 healthy controls were enrolled in this study. 11KTRs were included in the SRL-based therapy group and the other 15 in the TAC-based therapy group. Flow cytometry was used to detect the percentages and absolute numbers of MDSCs, T cell populations, HLA-DR monocytes, neutrophil CD64 index, and cytokines in peripheral blood.

RESULTS

In KTRs, the expression of G-MDSCs and M-MDSCs was significantly higher than the HCs, while the expression of HLA-DR monocytes, CD38/CD28 activated T cells, CD4 naïve T cells, CD4 effector memory T cells, and central memory T cells were significantly lower. The use of mTOR inhibitors in KTRs induced changes in the distribution of activated and naïve-memory T cell subsets and decreased proinflammatory cytokines.

DISCUSSION

In KTRs, G-MDSCs and M-MDSCs accumulated while functionally activated, naïve-memory T cell populations and HLA-DR monocytes markedly decreased one year after transplantation. Additionally, the number of MDSCs and T cell subsets following transplantation is likely regulated by mTOR inhibitors.

摘要

背景

对肾移植受者(KTRs)在不同免疫抑制治疗下进行全面的外周免疫细胞特征分析,包括新型免疫抑制亚群髓源性抑制细胞(MDSCs),有助于:1)评估免疫抑制状况和移植物接受情况;2)提示感染和排斥反应的出现;3)选择有益的免疫抑制方案。

方法

本研究纳入了26例平均移植时间为360天的KTRs和13名健康对照者。基于西罗莫司(SRL)治疗组纳入11例KTRs,基于他克莫司(TAC)治疗组纳入另外15例。采用流式细胞术检测外周血中MDSCs、T细胞亚群、HLA-DR单核细胞、中性粒细胞CD64指数和细胞因子的百分比及绝对数量。

结果

KTRs中,粒细胞-髓源性抑制细胞(G-MDSCs)和单核细胞-髓源性抑制细胞(M-MDSCs)的表达显著高于健康对照者(HCs),而HLA-DR单核细胞、CD38/CD28活化T细胞、CD4初始T细胞、CD4效应记忆T细胞和中枢记忆T细胞的表达显著降低。KTRs中使用雷帕霉素靶蛋白(mTOR)抑制剂可诱导活化和初始-记忆T细胞亚群分布的变化,并降低促炎细胞因子水平。

讨论

在KTRs中,移植后1年G-MDSCs和M-MDSCs积累且功能活化,而初始-记忆T细胞群体和HLA-DR单核细胞显著减少。此外,移植后MDSCs和T细胞亚群的数量可能受mTOR抑制剂调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ffa/12187787/7966ffc38354/fimmu-16-1605664-g001.jpg

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