scholarly journals Peripheral Blood from Rheumatoid Arthritis Patients Shows Decreased Treg CD25 Expression and Reduced Frequency of Effector Treg Subpopulation

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 801
Author(s):  
Eunbyeol Go ◽  
Su-Jin Yoo ◽  
Suyoung Choi ◽  
Pureum Sun ◽  
Min Kyung Jung ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Treg Cells ◽  
Joint Function ◽  
Treg Frequency ◽  
Cd25 Expression ◽  
Reduced Frequency ◽  
Treg Population ◽  
And Control

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by immune cell infiltration of the synovium, leading to the loss of cartilage, bone, and joint function. Although regulatory T (Treg) cells are thought to modulate the initiation and progression of RA, a consensus has yet to be reached regarding the function and composition of Treg cells in RA patients. To address these discrepancies, we analyzed not only the total Treg frequency but also that of Treg subpopulations in the peripheral blood of RA patients and healthy controls by flow cytometry. We found that the total Treg population was not significantly different between RA and control subjects. However, the effector Treg cell subgroup, defined as CD45RA−CD25hi, showed markedly decreased frequency in RA patients. In addition, the total Treg population from RA patients showed a significant decline in the expression of CD25. Both the naïve and effector Treg subgroups also showed marked reduction of CD25 expression in RA patients compared to controls. These data suggest that the decreased frequency of effector Treg cells and overall reduction of CD25 expression in Treg cells in the peripheral blood may be evidence of altered Treg homeostasis associated with RA pathogenesis.

scholarly journals Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 245
Author(s):  
Daniil Shevyrev ◽  
Valeriy Tereshchenko ◽  
Elena Blinova ◽  
Nadezda Knauer ◽  
Ekaterina Pashkina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Peripheral Blood ◽  
Treg Cells ◽  
Homeostatic Proliferation ◽  
Suppressive Activity ◽  
Healthy Donors

Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4+ and CD8+ cells. The phenotype and proliferation of purified CD3+CD4+CD25+CD127lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia.

scholarly journals Therapeutic Effect of Exogenous Treg Cells on Collagen-Induced Arthritis and Rheumatoid Arthritis

2019 ◽  
Author(s):  
Shutong Li ◽  
Hongxing Wang ◽  
Hui Wu ◽  
Guoqing Zhang ◽  
Xiaotian Chang
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometry ◽  
Peripheral Blood ◽  
Synovial Fibroblast ◽  
Treg Cells ◽  
Cell Counting ◽  
Fibroblast Cells ◽  
Collagen Induced Arthritis ◽  
Gm Csf

Abstract Background Regulatory T (Treg) cells have anti-inflammatory and anti-autoimmune functions. The proportion and functions of Treg cells are perturbed in rheumatoid arthritis (RA) patients. Methods Human Treg cells were induced to amplify in vitro and cocultured with RA synovial fibroblast cells (RASFs). The proliferation and apoptosis of RASFs were determined by the cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Human Treg cells were also injected to collagen-induced arthritis (CIA) rats via the tail vein. Changes in lymphocyte subtypes and cytokines in the peripheral blood and spleen were observed by flow cytometry. Results After coculture with the Treg cells, the proliferation of RA synovial fibroblast cells decreased (p<0.01), and the rate of apoptosis increased (p=0.037). The human Treg cells were injected into the tail veins of collagen-induced arthritis (CIA) rats. The severity of the CIA was reduced (p<0.01) following the injection, the percentages of rat endogenous Treg cells in the peripheral blood and spleen increased significantly (p=0.007 and p<0.01, respectively), and the proportion of B cells decreased (p=0.031). The levels of interleukin IL-5 and IL-6 and the Th1/Th2 ratio in the peripheral blood were significantly decreased (p=0.013, 0.009 and 0.012, respectively). The number of NK cells and the levels of IL-4, IL-13, TNF-α, IFN-γ and GM-CSF in the peripheral blood and spleen did not change significantly. Conclusion These results suggest that exogenous Treg cells play a therapeutic role in RA and CIA. Treg cell treatment could serve as a therapy for RA.

Analysis of regulatory T cells in patients of NSCLC with malignant pleural effusion.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17511-e17511
Author(s):  
Prabhat Singh Malik ◽  
Vinod Raina ◽  
Amar Singh ◽  
Dipendrea Kumar Mitra
Keyword(s):  
T Cells ◽  
Pleural Effusion ◽  
Peripheral Blood ◽  
Chemokine Receptors ◽  
Malignant Pleural Effusion ◽  
Advanced Nsclc ◽  
Treg Cells ◽  
Healthy Controls ◽  
Anatomic Site ◽  
Treg Frequency

e17511 Background: Enrichment of regulatory T (Treg) cells at the affected anatomic site in cancer may suppress the anti-tumor immune response influencing the cancer progression. Understanding of the clinical relevance of Treg mediated suppression of anti-tumor immune response and mechanisms underlying their preferential trafficking to the affected anatomic site is still limited. The aim of this study was to enumerate the frequencies of Treg cells in malignant pleural effusion and peripheral blood of patients with advanced NSCLC and it’s trend after treatment. Methods: Treg frequencies were evaluated in pleural effusion and peripheral blood of the patients with advanced NSCLC (n=27) using flowcytometry and compared with peripheral blood of age and sex matched healthy controls (n=15) and tubercular pleural effusions (n=10). The Treg cells were characterized as CD4+CD25+Foxp3+ T cells gated on CD4+CD25+ T cells. We assessed the effect of treatment response on Treg frequency. We have also looked for the expression of chemokine receptors CCR4 and CCR6 on the Tregs in pleural effusion and peripheral blood of the patients. Results: Compared to healthy controls, frequency of CD4+CD25+Foxp3+ Tregs was significantly increased in peripheral blood of patients with NSCLC (p=0.0036). In pleural effusion of patients, Treg frequency was higher than their corresponding peripheral blood (p=0.025). As compared to tubercular pleural effusion Treg frequency was higher in malignant effusion (p<0.0001). We had 12 patients who completed treatment and in whom response evaluation was available. Treg frequency reduced at the time of response (PR or SD) and increased again at disease progression. Surface expression of CCR4 and CCR6 was higher on Treg cells as compared to non Treg CD4 cells among the patients (p=0.0001; p=0.001 respectively). However, there was no difference in expression of these chemokine receptors on Tregs in pleural fluid and peripheral blood. Conclusions: Tregs are increased in patients of NSCLC, both at disease site and in systemic circulation. This increase may be chemokine receptors mediated. Treg frequency changes with treatment and response. Modulation of Tregs may have therapeutic implication in the management of advanced NSCLC.

scholarly journals New Insights about Treg and Th17 Cells in HIV Infection and Disease Progression

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Jacqueline María Valverde-Villegas ◽  
Maria Cristina Cotta Matte ◽  
Rúbia Marília de Medeiros ◽  
José Artur Bogo Chies
Keyword(s):  
Hiv Infection ◽  
Disease Progression ◽  
Th17 Cells ◽  
Immune Cell ◽  
Treg Cells ◽  
Proinflammatory Response ◽  
Effector Cells ◽  
T Effector Cells ◽  
Self Tolerance ◽  
And Control

Treg and Th17 cell subsets are characterized by the expression of specific transcriptional factors and chemokine receptor as well as by secretion of specific cytokine and chemokines. These subsets are important to the differentiation, expansion, homing capacity, and recruitment of several different immune cell populations to the site of infection. Whereas Treg cells maintain self-tolerance and control the activation and expansion of autoreactive CD4+T effector cells through an anti-inflammatory response, Th17 cells, in an exacerbated unregulated proinflammatory response, can promote autoimmunity. Despite such apparently opposite functions, Th17 and Treg cells share common characteristics, and their differentiation pathways are interconnected. Recent studies have revealed quite intricate relations between Treg and Th17 cells in HIV infection and progression to AIDS. Considering Treg cells, different subsets were already investigated in the context of HIV infection, indicating a fluctuation in the total number and frequency throughout the disease course. This review focuses on the recent findings regarding the role of regulatory T and Th17 cells in the context of HIV infection, highlighting the importance of the balance between these two subsets on disease progression.

scholarly journals CD4+CD25highCD127low/- Treg Cell Frequency from Peripheral Blood Correlates with Disease Activity in Patients with Rheumatoid Arthritis

2011 ◽  
Vol 38 (12) ◽  
pp. 2517-2521 ◽  
Author(s):  
SHIN-YA KAWASHIRI ◽  
ATSUSHI KAWAKAMI ◽  
AKITOMO OKADA ◽  
TOMOHIRO KOGA ◽  
MAMI TAMAI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treg Cell ◽  
Peripheral Blood ◽  
Treg Cells ◽  
Clinical Disease ◽  
Joint Disease ◽  
Healthy Controls ◽  
Cell Frequency ◽  
Clinical Disease Activity

Objective.To investigate whether the frequency of peripheral blood (PB) regulatory T cells (Treg) correlates with the clinical disease activity of rheumatoid arthritis (RA).Methods.PB Treg cells, defined as the CD4+CD25highCD127low/- population, were examined by flow cytometry in 48 patients with RA, including 13 who had never received disease-modifying antirheumatic drugs (DMARD), 19 with active disease who were receiving (n = 14) or had received (n = 5) DMARD, and 16 receiving DMARD whose disease was in remission. The clinical disease activity of the patients was defined by the 28-joint Disease Activity Score (DAS28). The association of DAS28, C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) with the frequency of PB Treg cells was examined.Results.The frequency of PB Treg cells in patients with RA was significantly low compared with that of healthy controls (n = 14). Among the 3 populations of patients with RA, Treg cell frequency was lowest in patients with active RA. In contrast, the Treg cell frequency of patients with RA in remission was similar to that of healthy controls. Accordingly, the frequency of CD4+CD25highCD127low/- Treg cells negatively correlated with DAS28, CRP, and ESR in patients with RA.Conclusion.The data suggest that Treg cells, defined as the CD4+CD25highCD127low/- population, may contribute to the pathogenesis of RA and be an indicator of disease activity.

scholarly journals The Association of Peripheral Blood Regulatory T-Cell Concentrations With Epithelial Ovarian Cancer: A Brief Report

2016 ◽  
Vol 27 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Rikki A. Cannioto ◽  
Lara E. Sucheston-Campbell ◽  
Shalaka Hampras ◽  
Ellen L. Goode ◽  
Keith Knutson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Confidence Interval ◽  
Epithelial Ovarian Cancer ◽  
Peripheral Blood ◽  
Odds Ratio ◽  
Treg Cells ◽  
Healthy Controls ◽  
Treg Frequency ◽  
History Of ◽  
History Of Cancer

ObjectiveThere is a mounting body of evidence demonstrating higher percentages of regulatory T (Treg) cells in the peripheral blood of patients with cancer in comparison to healthy controls, but there is a paucity of epidemiological literature characterizing circulating Treg cells among patients with epithelial ovarian cancer (EOC). To investigate the role of peripheral Treg cells in ovarian neoplasms, we conducted a case–control study to characterize circulating concentrations of Treg cells among patients with EOC, women with benign ovarian conditions, and healthy controls without a history of cancer.Materials and MethodsParticipants were identified for inclusion due to their participation in the Data Bank and BioRepository program at Roswell Park Cancer Institute in Buffalo, NY. Patients included 71 women with a primary diagnosis of EOC and 195 women with a diagnosis of benign ovarian conditions. Controls included 101 age- and race-matched women without a history of cancer. Nonfasting, pretreatment peripheral blood levels of CD3+CD4+CD25+FOXP3+ Treg cells were measured using flow cytometric analyses and expressed as a percentage of total CD3+ cells and as a percentage of total CD3+CD4+ cells.ResultsCompared to healthy controls and women with benign ovarian conditions, patients with EOC had significantly higher frequency of Treg cells (P < 0.04). In multivariable logistic regression analyses using Treg frequency expressed as a percentage of CD+3 cells, we observed a significant positive association between Treg cell percentage and EOC risk, with each 1% increase associated with a 37% increased risk of EOC (odds ratio, 1.37; 95% confidence interval, 1.04–1.80). We observed a similar trend when Treg frequency was expressed as a percentage of CD3+CD+4 cells (odds ratio, 1.22; 95% confidence interval, 0.99–1.49).ConclusionsThe current study provides support that peripheral Treg cell frequency is elevated in patients with EOC in comparison to women with benign ovarian conditions and healthy controls.

scholarly journals Investigating the Balance between Th17/Treg Cells in Rheumatoid Arthritis and its Association with Disease Activity

2019 ◽  
Vol 09 (01) ◽  
pp. e75-e83
Author(s):  
Hanan Aly Taha ◽  
Walaa G. Hozayen ◽  
Ahmed Mohamed Okasha ◽  
Amr E. Ahmed ◽  
Manar Ali A. Shata ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Complete Blood Count ◽  
Active Form ◽  
Joint Destruction ◽  
Treg Cells ◽  
Inactive Disease ◽  
Humoral And Cellular Immunity ◽  
Significant Difference ◽  
And Control

AbstractRheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by articular inflammation and joint destruction. The mechanism of RA pathogenesis is not fully understood, but humoral and cellular immunity are known to be involved. CD4+ T lymphocytes and cytokines released by these cells are suggested to initiate inflammation in RA. This study aimed to assess T helper 17 (Th17)/regulatory T (Treg) cell ratio and its correlation with disease activity in adult and juvenile RA. This study included 80 patients, with RA, including 40 adults (mean age: 36.4 ± 11.1 years and 40 juveniles mean age: 12.7 ± 2.2 years), and 80 healthy controls. For all patients and control subjects, patient and disease characteristics; laboratory tests for complete blood count, erythrocyte sedimentation rate, C-reactive protein (CRP), rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP), anti-nuclear antibodies (ANA), and flow cytometry to determine the numbers of Th17 and Treg cells. There was a statistically significant increase in the Th17/Treg ratio in patients with active disease compared with those with inactive disease for both adult and juvenile RA compared with controls. However, a similar significant difference was not observed between those with inactive adult and juvenile RA and controls. There were significant positive correlations between the Th17/Treg ratio and disease activity score 28 (DAS28), CRP, anti-CCP, and ANA in active adult and juvenile RA. The Th17/Treg ratio was increased in active form of adult and juvenile RA compared with inactive RA and control, indicating the Th17/Treg ratio as a potentially useful marker of disease activity.

scholarly journals Therapeutic Effect of Exogenous Regulatory T Cells on Collagen-induced Arthritis and Rheumatoid Arthritis

2020 ◽  
Vol 29 ◽  
pp. 096368972095413
Author(s):  
Shutong Li ◽  
Hongxing Wang ◽  
Hui Wu ◽  
Xiaotian Chang
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
Cell Transplantation ◽  
Treg Cell ◽  
Therapeutic Effect ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Treg Cells ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis

Regulatory T (Treg) cells have anti-inflammatory functions and heighten immune tolerance. The proportion and functions of Treg cells are perturbed in rheumatoid arthritis (RA), contributing to the excessive immune activation associated with this disease. We therefore hypothesized that supplementation with foreign Treg cells could be used to treat RA. To investigate the therapeutic effects of exogenous Treg cells on RA and its mechanism, we used human Treg cells to treat collagen-induced arthritis (CIA) in a rat model to observe whether exogenous Treg cells can treat the disease across species. Successful treatment would indicate that Treg cell transplantation in humans is more likely to affect RA. In the present study, human Treg cells were collected from healthy human peripheral blood and culture-expanded in vitro. Induced human Treg cells were injected into CIA rats via the tail vein. The rats’ lymphocyte subtypes, cytokines, and Th1/Th2 ratios were measured using flow cytometry. In the rats, following injection of the human Treg cells, the severity of CIA was significantly reduced ( P < 0.01), the proportion of endogenous Treg cells increased in the peripheral blood and spleen ( P = 0.007 and P < 0.01, respectively), and the proportion of B cells decreased ( P = 0.031). The IL-5 level, IL-6 level, and Th1/Th2 ratio in the peripheral blood were decreased ( P = 0.013, 0.009, and 0.012, respectively). The culture-expanded human Treg cells were also cultured with synovial fibroblast cells from RA patients (RASFs). After coculture with Treg cells, RASFs showed reduced proliferation ( P < 0.01) and increased apoptosis ( P = 0.037). These results suggest that exogenous and induced Treg cells can produce a therapeutic effect in RA and CIA by increasing endogenous Treg cells and RASF apoptosis and reducing B cells, the Th1/Th2 ratio, and secretion levels of IL-5 and IL-6. Treg cell transplantation could serve as a therapy for RA that does not cause immune rejection.

scholarly journals Regulatory T cells in rheumatoid arthritis showed increased plasticity toward Th17 but retained suppressive function in peripheral blood

2014 ◽  
Vol 74 (6) ◽  
pp. 1293-1301 ◽  
Author(s):  
Tian Wang ◽  
Xiaolin Sun ◽  
Jing Zhao ◽  
Jing Zhang ◽  
Huaqun Zhu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Negative Regulator ◽  
Suppressive Function ◽  
Treg Population ◽  
Treg Subset

ObjectiveRegulatory T cells (Tregs) with the plasticity of producing proinflammatory cytokine IL-17 have been demonstrated under normal and pathogenic conditions. However, it remains unclear whether IL-17-producing Tregs lose their suppressive functions because of their plasticity toward Th17 in autoimmunity. The aim of this study was to investigate IL-17-producing Tregs from patients with rheumatoid arthritis (RA), and characterise their regulatory capacity and clinical significance.MethodsFoxp3 and IL-17 coexpression were evaluated in CD4 T lymphocytes from RA patients. An in vitro T cell polarisation assay was performed to investigate the role of proinflammatory cytokines in IL-17-producing Treg polarisation. The suppressive function of IL-17-producing Tregs in RA was assessed by an in vitro suppression assay. The relationship between this Treg subset and clinical features in RA patients was analysed using Spearman's rank correlation test.ResultsA higher frequency of IL-17-producing Tregs was present in the peripheral blood of RA patients compared with healthy subjects. These cells from peripheral blood showed phenotypic characteristics of Th17 and Treg cells, and suppressed T cell proliferation in vitro. Tregs in RA synovial fluid lost suppressive function. The Th17 plasticity of Tregs could be induced by IL-6 and IL-23. An increased ratio of this Treg subset was associated with decreased levels of inflammatory markers, including the erythrocyte sedimentation rate and C-reactive protein level, in patients with RA.ConclusionsIncreased levels of IL-17-producing Tregs were identified in RA patients. This Treg subset with Th17 plasticity in peripheral blood retained suppressive functions and was associated with milder inflammatory conditions, suggesting that this Treg population works as a negative regulator in RA, but in RA synovial site it may be pathogenic.

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