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免疫相关性血细胞减少症患者中 CD4+ T 淋巴细胞数量异常和 CD4+ T 淋巴细胞分泌的细胞因子表达异常。

Abnormal numbers of CD4+ T lymphocytes and abnormal expression of CD4+ T lymphocyte‑secreted cytokines in patients with immune‑related haemocytopenia.

机构信息

Department of Haematology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

出版信息

Mol Med Rep. 2019 Nov;20(5):3979-3990. doi: 10.3892/mmr.2019.10663. Epub 2019 Sep 10.

DOI:10.3892/mmr.2019.10663
PMID:31545490
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6797981/
Abstract

In the past decade, a group of cases with persisting haemocytopenia were separated from those with idiopathic cytopenia of undetermined significance due to the optimal response of these patients to immunosuppression therapy and due to the detection of autoantibodies in the bone marrow of haemopoietic cells. This condition was termed immune‑related haemocytopenia (IRH). However, the quantity of T lymphocytes remained unknown. In the present study, the percentage of CD4+ T‑cell subsets and related cytokines was measured using flow cytometry and an enzyme‑linked immunosorbent assay. An abnormal number of CD4+ T cell subsets was found, including increased percentages of T helper (Th)2, Th9 and Th17 cells and a decreased number of regulatory T (Treg) cells. In addition, the results showed downregulation in the levels of interleukin (IL)‑2, transforming growth factor‑β and IL‑35, and upregulation in the levels of IL‑4, IL‑6, IL‑17, IL‑23 and interferon‑γ in patients who did not receive therapy (untreated patients). These levels were significantly associated with the number of peripheral blood cells and were recovered following treatment. In conclusion, an abnormal number of CD4+ T cell subsets and corresponding abnormal levels of regulatory cytokines resulted in the stimulation of B1 lymphocytes to produce autoantibodies in IRH, which may be considered as markers to evaluate disease prognosis and treatment strategies.

摘要

在过去的十年中,由于这些患者对免疫抑制治疗的最佳反应以及在造血细胞骨髓中检测到自身抗体,将一组持续存在血细胞减少的病例与特发性血细胞减少症的不明原因病例分开。这种情况被称为免疫相关血细胞减少症(IRH)。但是,T 淋巴细胞的数量仍然未知。在本研究中,使用流式细胞术和酶联免疫吸附试验测量了 CD4+ T 细胞亚群和相关细胞因子的百分比。发现 CD4+ T 细胞亚群数量异常,包括辅助性 T 细胞(Th)2、Th9 和 Th17 细胞的百分比增加,调节性 T(Treg)细胞数量减少。此外,结果表明,未经治疗(未治疗患者)的患者中白细胞介素(IL)-2、转化生长因子-β和 IL-35 的水平下调,IL-4、IL-6、IL-17、IL-23 和干扰素-γ的水平上调。这些水平与外周血细胞数量显著相关,并在治疗后恢复。总之,CD4+ T 细胞亚群数量异常和相应的调节性细胞因子水平异常导致 B1 淋巴细胞产生自身抗体,这可能被认为是评估疾病预后和治疗策略的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3136/6797981/767cfbfe759e/MMR-20-05-3979-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3136/6797981/8bc5a45141df/MMR-20-05-3979-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3136/6797981/2bd0647bb2c7/MMR-20-05-3979-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3136/6797981/411e34d64731/MMR-20-05-3979-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3136/6797981/82cec77304de/MMR-20-05-3979-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3136/6797981/767cfbfe759e/MMR-20-05-3979-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3136/6797981/8bc5a45141df/MMR-20-05-3979-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3136/6797981/2bd0647bb2c7/MMR-20-05-3979-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3136/6797981/411e34d64731/MMR-20-05-3979-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3136/6797981/82cec77304de/MMR-20-05-3979-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3136/6797981/767cfbfe759e/MMR-20-05-3979-g04.jpg

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