类风湿关节炎患者 T 细胞及可溶性蛋白的综合共抑制受体（Co-IR）表达。

Comprehensive Co-Inhibitory Receptor (Co-IR) Expression on T Cells and Soluble Proteins in Rheumatoid Arthritis.

机构信息

Department of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33302, Taiwan.

Division of Allergy, Immunology and Rheumatology, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin St. Kwei-Shan, Taoyuan 33305, Taiwan.

出版信息

Cells. 2024 Feb 26;13(5):403. doi: 10.3390/cells13050403.

DOI:10.3390/cells13050403

PMID:38474367

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10931001/

Abstract

UNLABELLED

Co-inhibitory receptors (Co-IRs) are essential in controlling the progression of immunopathology in rheumatoid arthritis (RA) by limiting T cell activation. The objective of this investigation was to determine the phenotypic expression of Co-IR T cells and to assess the levels of serum soluble PD-1, PDL-2, and TIM3 in Taiwanese RA patients.

METHODS

Co-IRs T cells were immunophenotyped employing multicolor flow cytometry, and ELISA was utilized for measuring soluble PD-1, PDL-2, and TIM3. Correlations have been detected across the percentage of T cells expressing Co-IRs (MFI) and different indicators in the blood, including ESR, high-sensitivity CRP (hsCRP), 28 joint disease activity scores (DAS28), and soluble PD-1/PDL-2/TIM3.

RESULTS

In RA patients, we recognized elevated levels of PD-1 (CD279), CTLA-4, and TIGIT in CD4+ T cells; TIGIT, HLA-DR, TIM3, and LAG3 in CD8+ T cells; and CD8+CD279+TIM3+, CD8+HLA-DR+CD38+ T cells. The following tests were revealed to be correlated with hsCRP: CD4/CD279 MFI, CD4/CD279%, CD4/TIM3%, CD8/TIM3%, CD8/TIM3 MFI, CD8/LAG3%, and CD8+HLA-DR+CD38+%. CD8/LAG3 and CD8/TIM3 MFIs are linked to ESR. DAS28-ESR and DAS28-CRP exhibited relationships with CD4/CD127 MFI, CD8/CD279%, and CD8/CD127 MFI, respectively. CD4+CD279+TIM3+% was correlated with DAS28-ESR ( = 0.0084, N = 46), DAS28-CRP ( = 0.007, N = 47), and hsCRP ( = 0.002, N = 56), respectively. In the serum of patients with RA, levels of soluble PD-1, PDL-2, and Tim3 were extremely elevated. CD4+ TIM3+% ( = 0.0089, N = 46) and CD8+ TIM3+% ( = 0.0305, N = 46) were correlated with sTIM3 levels; sPD1 levels were correlated with CD4+CD279+% ( < 0.0001, N = 31) and CD3+CD279+% ( = 0.0084, N = 30).

CONCLUSIONS

Co-IR expressions on CD4+ and CD8+ T cells, as well as soluble PD-1, PDL-2, and TIM3 levels, could function as indicators of disease activity and potentially play crucial roles in the pathogenesis of RA.

摘要

目的

确定台湾地区类风湿关节炎（RA）患者中抑制性受体（Co-IR）T 细胞的表型表达，并评估血清可溶性 PD-1、PDL-2 和 TIM3 水平。

方法

采用多色流式细胞术对 Co-IRs T 细胞进行免疫表型分析，采用 ELISA 法检测可溶性 PD-1、PDL-2 和 TIM3。检测 Co-IRs T 细胞表达的 T 细胞（MFI）百分比与血液中不同指标（ESR、高敏 CRP[hsCRP]、28 关节疾病活动评分[DAS28]和可溶性 PD-1/PDL-2/TIM3）之间的相关性。

结果

在 RA 患者中，我们发现 CD4+T 细胞中 PD-1（CD279）、CTLA-4 和 TIGIT 水平升高；CD8+T 细胞中 TIGIT、HLA-DR、TIM3 和 LAG3 水平升高；CD8+CD279+TIM3+、CD8+HLA-DR+CD38+T 细胞中 CD8+CD279+TIM3+、CD8+HLA-DR+CD38+T 细胞中 CD8+CD279+TIM3+。hsCRP 与 CD4/CD279 MFI、CD4/CD279%、CD4/TIM3%、CD8/TIM3%、CD8/TIM3 MFI、CD8/LAG3%和 CD8+HLA-DR+CD38+%相关。CD8/LAG3 和 CD8/TIM3 MFI 与 ESR 相关。DAS28-ESR 和 DAS28-CRP 与 CD4/CD127 MFI、CD8/CD279%和 CD8/CD127 MFI 分别相关。CD4+CD279+TIM3+%与 DAS28-ESR（=0.0084，N=46）、DAS28-CRP（=0.007，N=47）和 hsCRP（=0.002，N=56）相关。RA 患者血清中可溶性 PD-1、PDL-2 和 Tim3 水平显著升高。CD4+TIM3+%（=0.0089，N=46）和 CD8+TIM3+%（=0.0305，N=46）与 sTIM3 水平相关；sPD1 水平与 CD4+CD279+%（<0.0001，N=31）和 CD3+CD279+%（=0.0084，N=30）相关。