scholarly journals CD39+ EXPRESSION BY REGULATORY T CELLS IN PULMONARY SARCOIDOSIS AND LOFGREN’S SYNDROME

2019 ◽  
Vol 21 (3) ◽  
pp. 467-478
Author(s):  
I. V. Kudryavtsev ◽  
N. M. Lazareva ◽  
O. P. Baranova ◽  
A. S. Golovkin ◽  
D. V. Isakov ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Relative Number ◽  
Epithelioid Cell ◽  
Pulmonary Sarcoidosis ◽  
Peripheral Blood Cell ◽  
Unknown Etiology ◽  
Löfgren’S Syndrome ◽  
Acute Form

Sarcoidosis is a disorder of unknown etiology characterized by development of necrosis-free epithelioid cell granulomas in various tissues. There are two main phenotypes of pulmonary sarcoidosis (PS): Lofgren’s syndrome (LS) is an acute form with favorable outcome, while non-Lofgren’s syndrome (nLS) is a chronic type of disease that can lead to pulmonary fibrosis in 20% of cases.Our study was aimed at investigating changes in the main cell-surface differentiation antigens on peripheral blood regulatory T cells (Tregs) from the patients with first diagnosed PS without treatment (LS, n = 11) and nLS (n = 46) compared to healthy volunteers (HC, n = 26).These indexes might be used as immunological markers for predicting severity of this disorder. Flow cytometry analysis of peripheral blood cell samples demonstrated that the nLS patients had decreased relative numbers of CD3+ cells vs healthy controls, as well as diminished CD3+CD4+ cells vs HC and LS patients. Furthermore, the relative and absolute Treg numbers were also decreased in nLS group vs HC (2.83% (2.47; 3.36) vs 3.33% (2.79; 3.84), p = 0.021), and 37 (29; 52) cells vs 50 (42; 65), p = 0.004, respectively) per one microliter of peripheral blood. Relative number of CD39-positive Тregs in chronic vs acute sarcoidosis patients was associated with 51.02% (38.20; 61.62) vs 48.64% (41.46; 63.72) that was significantly (p < 0.001 and p = 0.007, respectively) higher than in HC (39.52% (11.55; 46.34). We have found that “naïve” (CD45R0-CD62L+) Тregs did not significantly differ in percentage of CD39- and CD73-positive cells in all the groups tested. Moreover, CD45R0+CD62L+ Тregs in LS and nLS patients contained significantly more CD39-positive cells (69.66% (61.92; 79.34) and 67.62% (61.92; 79.34), respectively, compared to 47.55% (15.74; 65.32) in HC (p < 0.001 and p = 0.004, respectively). In case of CD45R0 + CD62LTregs able to exit from the circulation and migrate to the site of inflammation, an increased percentage of CD39-positive subset was noted only in patients with chronic sarcoidosis and HC (61.79% (55.12; 73.09) and 57.27% (16.03; 66.98), p = 0.006). Enhanced CD39 expression on Tregs seems to be related to chronic immune response, so that antigen elimination becomes impossible due to Treg overactivation, as shown in patients with sarcoidosis and some other chronic autoimmune and infectious disorders.

scholarly journals Intracellular cytokine repertoire in different T cell subsets from patients with sarcoidosis

Thorax ◽  
2001 ◽  
Vol 56 (6) ◽  
pp. 487-493
Author(s):  
M Möllers ◽  
S P Aries ◽  
D Drömann ◽  
B Mascher ◽  
J Braun ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Disease ◽  
Peripheral Blood ◽  
Pulmonary Sarcoidosis ◽  
T Cell Subsets ◽  
Course Of Disease ◽  
Tnf Α ◽  
Intracellular Expression ◽  
Necrosis Factor ◽  
Memory Lymphocytes

BACKGROUNDPulmonary sarcoidosis is characterised by a mononuclear alveolitis with a predominance of CD4+ T cells and macrophages. We determined the intracellular expression of interferon (IFN)γ, interleukin (IL)-2, tumour necrosis factor (TNF)α, IL-4, IL-5 and IL-10 in CD4+ and CD8+, naive and memory lymphocytes from blood and bronchoalveolar lavage (BAL) fluid using three colour flow cytometry.METHODSEighteen untreated patients with pulmonary sarcoidosis were evaluated and stratified according to whether they had acute or chronic disease.RESULTSSignificantly more T cells expressed Th1 than Th2 type cytokines in both BAL fluid and peripheral blood samples, regardless of clinical presentation. Significantly greater proportions of T cells secreted Th1 type cytokines in BAL fluid than in peripheral blood. Th1 type cytokines were more frequently expressed by peripheral and alveolar T cells in acute disease than in chronic disease. There were no significant differences between CD4+ and CD8+ T cells. Concerning naive and memory lymphocytes, significantly higher CD45RO:CD45RA ratios were found in BAL fluid than in blood, and increased expression of Th2 type cytokines was found in peripheral compared with alveolar memory T cells.CONCLUSIONSOur data support the immunopathogenetic concept of Th1/Th2 imbalance and compartmentalisation in pulmonary sarcoidosis and suggest that the cytokine patterns change during the course of disease. Expression of Th2 type cytokines in memory lymphocytes is decreased in the alveolar compartment compared with peripheral blood.

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 Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 826-832
Author(s):  
Jiarong Wang ◽  
Liansheng Qiu ◽  
Yimin Chen ◽  
Minyun Chen
Keyword(s):  
T Cells ◽  
Allergic Rhinitis ◽  
Retrospective Study ◽  
Regulatory T Cells ◽  
Visual Analog Scale ◽  
Peripheral Blood ◽  
Sublingual Immunotherapy ◽  
Analog Scale ◽  
Vas Score ◽  
Medication Score

Abstract Background Few studies investigated the effects of sublingual immunotherapy (SLIT) on the peripheral regulatory T cells (Tregs)/Th17 ratio. Objective To investigate the effectiveness of SLIT in children with allergic rhinitis (AR) and the effects on the Tregs/Th17 ratio. Methods This was a retrospective study of children who were treated for AR between April 2017 and March 2018 at one hospital. The patients were grouped according to the treatments they received: SLIT + pharmacotherapy vs pharmacotherapy alone. Results Eighty children (51 boys and 29 girls; 40/group) were included. The visual analog scale (VAS) and medication scores at 1 year in the SLIT + pharmacotherapy group were 2.70 ± 1.08 and 1.1 ± 0.8, respectively, which were lower than at baseline (7.7 ± 1.2 and 3.6 ± 1.0, respectively) (both Ps < 0.05). For the pharmacotherapy group, the VAS score was decreased at 1 year vs baseline (3.3 ± 1.2 vs 7.4 ± 1.0; P < 0.05), but the medication score did not change (P > 0.05). In the SLIT + pharmacotherapy group, the Treg percentage increased, while the Th17 percentage decreased at 1 year (both Ps < 0.01). The percentages of Tregs and Th17s did not change in the pharmacotherapy group (both Ps > 0.05). Conclusions SLIT + pharmacotherapy can increase the Treg percentage and decrease the Th17 percentage in the peripheral blood of children with AR.

scholarly journals Isolation of functional human regulatory T cells (Treg) from the peripheral blood based on the CD39 expression

2009 ◽  
Vol 346 (1-2) ◽  
pp. 55-63 ◽  
Author(s):  
Magis Mandapathil ◽  
Stephan Lang ◽  
Elieser Gorelik ◽  
Theresa L. Whiteside
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Peripheral Blood

Expansion of CD4+CD25+FOXP3+ Regulatory T Cells in Peripheral Blood and Skin Lesions of Patients with Atopic Dermatitis

2008 ◽  
Vol 121 (2) ◽  
pp. S15-S15
Author(s):  
Y ITO ◽  
T MAKINO ◽  
Y ADACHI ◽  
H HIGASHIYAMA ◽  
T SHIMIZU ◽  
...  
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Skin Lesions

Low Frequency of Regulatory T Cells in the Peripheral Blood of Children with Type 1 Diabetes Diagnosed under the Age of Five

2012 ◽  
Vol 60 (4) ◽  
pp. 307-313 ◽  
Author(s):  
Agnieszka Szypowska ◽  
Anna Stelmaszczyk-Emmel ◽  
Urszula Demkow ◽  
Włodzimierz Łuczyński
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Low Frequency

Detection of CD4+CD25+FOXP3+ regulatory T cells in peripheral blood of patients with chronic autoimmune urticaria

2010 ◽  
Vol 52 (3) ◽  
pp. e15-e18 ◽  
Author(s):  
Ren-Shan Sun ◽  
Jian-Feng Sui ◽  
Xiao-Hong Chen ◽  
Xin-Ze Ran ◽  
Zi-Feng Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Autoimmune Urticaria

Potential use of biomarkers for the clinical evaluation of sarcoidosis

2021 ◽  
pp. jim-2020-001659
Author(s):  
Amir Mousapasandi ◽  
Cristan Herbert ◽  
Paul Thomas
Keyword(s):  
Clinical Evaluation ◽  
Clinical Presentation ◽  
Current Knowledge ◽  
Epithelioid Cell ◽  
Pulmonary Sarcoidosis ◽  
Biological Molecules ◽  
Unknown Etiology ◽  
Chronic Antigenic Stimulation ◽  
Host Genetic ◽  
Potential Use

Sarcoidosis is a systemic granulomatous disease of unknown etiology and pathogenesis with a heterogeneous clinical presentation. In the appropriate clinical and radiological context and with the exclusion of other diagnoses, the disease is characterized by the pathological presence of non-caseating epithelioid cell granulomas. Sarcoidosis is postulated to be a multifactorial disease caused by chronic antigenic stimulation. The immunopathogenesis of sarcoidosis encompasses a complex interaction between the host, genetic factors and postulated environmental and infectious triggers, which result in granuloma development.The exact pathogenesis of the disease has yet to be elucidated, but some of the inflammatory pathways that play a key role in disease progression and outcomes are becoming apparent, and these may form the logical basis for selecting potential biomarkers.Biomarkers are biological molecules that are altered pathologically. To date, there exists no single reliable biomarker for the evaluation of sarcoidosis, either diagnostically or prognostically but new candidates are emerging. A diagnosis of sarcoidosis ideally requires a biopsy confirming non-caseating granulomas, but the likelihood of progression that requires intervention remains unpredictable. These challenging aspects could be potentially resolved by incorporating biomarkers into clinical practice for both diagnosis and monitoring disease activity.This review outlines the current knowledge on sarcoidosis with an emphasis on pulmonary sarcoidosis, and delineates the understanding surrounding the implication of biomarkers for the clinical evaluation of sarcoidosis.

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