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Tim-3 和 CD39 的表达而非 PD1 的表达可定义危重症 COVID-19 患者中的 CD8 T 细胞。

Pronounce expression of Tim-3 and CD39 but not PD1 defines CD8 T cells in critical Covid-19 patients.

机构信息

Immunoregulation Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.

出版信息

Microb Pathog. 2021 Apr;153:104779. doi: 10.1016/j.micpath.2021.104779. Epub 2021 Feb 4.

Abstract

BACKGROUND

During viral infection, inhibitory receptors play a key role in regulating CD8 T-cell activity. The objective of this research was to investigate programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3), and CD39 exhaustion markers in CD8 T cells of new coronavirus disease-2019 (COVID-19) patients.

METHODS

A total of 44 patients with COVID-19 (17 subjects in a critical group and 27 patients in a non-critical group) and 14 healthy controls, who were admitted to Hospitals in Babol, were recruited to the study. In subjects' peripheral blood mononuclear cells (PBMCs), we compared the phenotype of CD8 T lymphocytes, expressing PD-1, TIM-3, or CD39, both alone and in various combinations.

RESULTS

The findings showed that the percentage of CD8 cells was significantly lower in patients. Critical and non-critical patients were more likely than healthy controls to have an escalated frequency of CD8 TIM-3, CD8 CD39, and CD8 TIM-3 CD39 cells. No significant differences were observed between all groups in the CD8 PD-1 cell counts. There was also no difference between three groups regarding the counts of CD8 TIM-3 PD-1, CD8 PD-1 CD39, and CD8 TIM-3 PD-1 CD39 cells. The counts of non-exhausted cells were significantly lower in critical and non-critical individuals compared to the healthy individuals' value.

CONCLUSION

Patients, infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), altered exhausted CD8 T lymphocytes with CD39 and TIM-3 exhaustion markers, which may account the dysregulated immune response found in COVID-19.

摘要

背景

在病毒感染过程中,抑制性受体在调节 CD8 T 细胞活性方面发挥着关键作用。本研究旨在探讨新型冠状病毒病 2019(COVID-19)患者 CD8 T 细胞中的程序性细胞死亡蛋白 1(PD-1)、T 细胞免疫球蛋白和粘蛋白结构域蛋白 3(TIM-3)和 CD39 耗竭标志物。

方法

共招募了 44 名 COVID-19 患者(重症组 17 例,非重症组 27 例)和 14 名健康对照者至巴布尔医院,比较了外周血单个核细胞(PBMCs)中 PD-1、TIM-3 或 CD39 单独表达和不同组合表达的 CD8 T 淋巴细胞表型。

结果

研究结果表明,患者的 CD8 细胞百分比明显较低。重症和非重症患者比健康对照组更有可能出现 CD8 TIM-3、CD8 CD39 和 CD8 TIM-3 CD39 细胞频率升高。三组间 CD8 PD-1 细胞计数无显著差异。三组间 CD8 TIM-3 PD-1、CD8 PD-1 CD39 和 CD8 TIM-3 PD-1 CD39 细胞计数也无差异。与健康对照组相比,重症和非重症个体的非耗竭细胞计数明显降低。

结论

感染严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的患者改变了 CD39 和 TIM-3 耗竭标志物的耗竭性 CD8 T 淋巴细胞,这可能解释了 COVID-19 中发现的免疫反应失调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aed/7857983/dd829bbe0a4f/gr1_lrg.jpg

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