A gene module associated with dysregulated TCR signaling pathways in CD4 + T cell subsets in rheumatoid arthritis

2018 ◽  
Vol 89 ◽  
pp. 21-29 ◽  
Author(s):  
Shuji Sumitomo ◽  
Yasuo Nagafuchi ◽  
Yumi Tsuchida ◽  
Haruka Tsuchiya ◽  
Mineto Ota ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Signaling Pathways ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Gene Module ◽  
Tcr Signaling

Loss of balance between protective and pro-inflammatory synovial tissue T-cell polyfunctionality predates clinical onset of rheumatoid arthritis

2021 ◽  
pp. annrheumdis-2021-220458
Author(s):  
Achilleas Floudas ◽  
Nuno Neto ◽  
Carl Orr ◽  
Mary Canavan ◽  
Phil Gallagher ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Synovial Tissue ◽  
Flow Cytometric Analysis ◽  
T Cell Responses ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Pathway Enrichment Analysis ◽  
Cell Responses

ObjectivesThis study investigates pathogenic and protective polyfunctional T-cell responses in patient with rheumatoid arthritis (RA), individuals at risk (IAR) and healthy control (HC) synovial-tissue biopsies and identifies the presence of a novel population of pathogenic polyfunctional T-cells that are enriched in the RA joint prior to the development of clinical inflammation.MethodsPathway enrichment analysis of previously obtained RNAseq data of synovial biopsies from RA (n=118), IAR (n=20) and HC (n=44) was performed. Single-cell synovial tissue suspensions from RA (n=10), IAR (n=7) and HC (n=7) and paired peripheral blood mononuclear cells (PBMC) were stimulated in vitro and polyfunctional synovial T-cell subsets examined by flow cytometric analysis, simplified presentation of incredibly complex evaluations (SPICE) and FlowSom clustering. Flow-imaging was utilised to confirm specific T-cell cluster identification. Fluorescent lifetime imaging microscopy (FLIM) was used to visualise metabolic status of sorted T-cell populations.ResultsIncreased plasticity of Tfh cells and CD4 T-cell polyfunctionality with enriched memory Treg cell responses was demonstrated in RA patient synovial tissue. Synovial-tissue RNAseq analysis reveals that enrichment in T-cell activation and differentiation pathways pre-dates the onset of RA. Switch from potentially protective IL-4 and granulocyte macrophage colony stimulating factor (GMCSF) dominated polyfunctional CD4 T-cell responses towards pathogenic polyfunctionality is evident in patient with IAR and RA synovial tissue. Cluster analysis reveals the accumulation of highly polyfunctional CD4+ CD8dim T-cells in IAR and RA but not HC synovial tissue. CD4+ CD8dim T-cells show increased utilisation of oxidative phosphorylation, a characteristic of metabolically primed memory T-cells. Frequency of synovial CD4+ CD8dim T-cells correlates with RA disease activity.ConclusionSwitch from potentially protective to pathogenic T-cell polyfunctionality pre-dates the onset of clinical inflammation and constitutes an opportunity for therapeutic intervention in RA.

Cell Surface CD28 Levels Define Four CD4+ T Cell Subsets: Abnormal Expression in Rheumatoid Arthritis

2001 ◽  
Vol 99 (2) ◽  
pp. 253-265 ◽  
Author(s):  
Laura-Inés Salazar-Fontana ◽  
Eva Sanz ◽  
Isabel Mérida ◽  
Antonio Zea ◽  
Ana Sanchez-Atrio ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Cell Surface ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Abnormal Expression

Comprehensive TCR repertoire analysis of CD4+ T-cell subsets in rheumatoid arthritis

2020 ◽  
Vol 109 ◽  
pp. 102432 ◽  
Author(s):  
Xu Jiang ◽  
Shiyu Wang ◽  
Chen Zhou ◽  
Jinghua Wu ◽  
Yuhao Jiao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Repertoire Analysis ◽  
Tcr Repertoire

scholarly journals Reduction of peripheral regulatory T cells in active rheumatoid arthritis patients with coronary artery disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanyan Wang ◽  
Rui Su ◽  
Baochen Li ◽  
Qiaoling Guo ◽  
Fangyuan Hu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Active Rheumatoid Arthritis ◽  
Absolute Number ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
The Absolute ◽  
Artery Disease

Abstract Objective To identify lymphocyte and CD4 + T cell subset characteristics, particularly regulatory T cells (Tregs), in active rheumatoid arthritis (RA) patients with coronary artery disease (CAD). Methods A total of 54 RA patients with CAD (RA-CAD group), 43 RA patients without CAD (pure RA group), and 43 healthy controls (HC group) were enrolled. The absolute number and frequency of lymphocyte subpopulations and CD4 + T cell subsets were analyzed by flow cytometry. Serum levels of cytokines were analyzed using a cytometric bead array. Clinical and laboratory data were collected retrospectively and their correlation with CD4 + T subsets were analyzed. Results There was a significant decrease in the absolute number of Treg cells (CD4 + CD25 + Foxp3 + T cells) in the RA-CAD group compared to the pure RA group (p < 0.001). Similarly, both the absolute number (p = 0.001) and frequency (p = 0.011) of Tregs in the RA-CAD group were decreased compared to the HCs, causing a Th17/Treg imbalance (p = 0.044). No difference was found in the absolute number and frequency of Treg cells between the pure RA and HC groups. However, the absolute Th17 cell count was increased in the pure RA group (p = 0.032). The serum level of cytokine IL-17 was lower in the RA-CAD group than in the pure RA group (p = 0.023). In the RA-CAD group, the Treg number was negatively correlated with the RA disease activity score and ESR value, and LDL and ApoB100 levels were negatively correlated with the number of Th17 cells. Conclusions Active RA patients with CAD sustain more severe immune tolerance damage and Th17/Treg disorder. Monitoring of lymphocyte and CD4 + T cell subsets, particularly Treg cells, is crucial to understanding immune status in this group. Focusing on RA activity and CAD risk control, immune-regulatory therapy based on the Treg level may be more beneficial for RA patients with CAD.

CD4+T-cell subsets in rheumatoid arthritis

2012 ◽  
Vol 7 (1) ◽  
pp. 37-53 ◽  
Author(s):  
Frederique Ponchel ◽  
Edward Vital ◽  
Sarah R Kingsbury ◽  
Yasser M El-Sherbiny
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Subsets ◽  
Cd4 T Cell
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