scholarly journals Imbalance of Th17 and T-regulatory cells in peripheral blood and synovial fluid in treatment naïve children with juvenile idiopathic arthritis

2014 ◽  
Vol 1 ◽  
pp. 71-76 ◽  
Author(s):  
Joanna Szymańska-Kałuża ◽  
Barbara Cebula-Obrzut ◽  
Piotr Smolewski ◽  
Jerzy Stanczyk ◽  
Elżbieta Smolewska
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Peripheral Blood ◽  
T Regulatory Cells ◽  
Regulatory Cells ◽  
Treatment Naïve

scholarly journals Peripheral regulatory T cells and anti-inflammatory cytokines in children with juvenile idiopathic arthritis

2018 ◽  
Vol 65 (1) ◽  
pp. 119-123 ◽  
Author(s):  
Katarzyna Sznurkowska ◽  
Małgorzata Boćkowska ◽  
Maciej Zieliński ◽  
Katarzyna Plata-Nazar ◽  
Piotr Trzonkowski ◽  
...  
Keyword(s):  
T Cells ◽  
Juvenile Idiopathic Arthritis ◽  
Inflammatory Cytokines ◽  
Peripheral Blood ◽  
T Regulatory Cells ◽  
Control Group ◽  
Healthy Children ◽  
Regulatory Cells ◽  
Color Flow ◽  
Anti Inflammatory

Background Juvenile idiopathic arthritis (JIA) is a chronic, heterogenous inflammatory disease of unclear pathogenesis. JIA is hypothesized to be linked to a defective immune regulation. Anti-inflammatory cytokines belong to the best known regulatory factors. T-regulatory cells are a crucial cellular component of immune tolerance. One of their functions is synthesis of interleukin 10 (IL-10) and transforming growth factor beta1 (TGF-ß1).The aim of this study was to determine the proportion of T-regulatory cells (CD4+CD25highFOXP3+) in peripheral blood, and serum levels of TGF-ß1 and IL-10 in patients with JIA.Methods: The study included 25 patients with newly diagnosed JIA: oligoarthritis (n=17) and polyarthritis (n=8). Control group was comprised of 17 healthy children. CD4+CD25highFOXP3+ T cells in peripheral blood were quantified by means of three-color flow cytometry. Serum concentrations of TGF-ß1 and IL-10 were estimated with ELISA.Results: The proportion of peripheral CD4+CD25highFOXP3+cells in patients with JIA was significantly higher than in the controls (p=0.04). The two groups did not differ significantly in terms of their TGF-ß1 and IL-10 concentrations.Conclusions: At the time of the diagnosis, children with JIA present with elevated proportion of T-regulatory cells (CD4+CD25highFOXP3+) in peripheral blood. Anti-inflammatory cytokines, IL-10 and TGF-ß1, are not upregulated in the serum of patients with JIA, and therefore should not be considered as biomarkers of this condition.

Th1 and Th17 Predominance in the Enthesitis-related Arthritis Form of Juvenile Idiopathic Arthritis

2009 ◽  
Vol 36 (8) ◽  
pp. 1730-1736 ◽  
Author(s):  
ANKIT MAHENDRA ◽  
RAMNATH MISRA ◽  
AMITA AGGARWAL
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Synovial Fluid ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Health Assessment ◽  
Treg Cells ◽  
Th2 Cells ◽  
Median Frequency ◽  
Enthesitis Related Arthritis

Objective.A Th1 biased immune response in synovial fluid has been reported in children with polyarticular and extended oligoarticular-type juvenile idiopathic arthritis (JIA). We investigated T cell phenotypes including Th1, Th2, Th17, and Treg with emphasis on Th17 and Treg, in order to differentiate cytokines in the enthesitis-related arthritis (ERA) form of JIA.Methods.The frequencies of Th1, Th2, Th17, and Treg cells were determined by flow cytometry in peripheral blood (PB) and synovial fluid from patients with ERA and healthy subjects. Levels of interleukin 1ß (IL-1ß), IL-6, IL-21, IL-23, and transforming growth factor ß (TGF-ß), cytokines that influence Th17 lineage cells, were measured in paired plasma and synovial fluid (SF) samples by ELISA. Frequencies are expressed as percentages and cytokine levels as pg/ml.Results.There were no differences in blood samples in the frequency of Th1, Th2, Th17, and Treg cells between patients and controls. In paired samples, the median frequency of CD4+IFN-γ+ (20.49 vs 4.03; p < 0.005) and CD4+IL-17+ (2.27 vs 0.57; p < 0.01) cells was significantly higher in SF compared to PB, respectively; whereas the frequency of CD4+IL-4+ (1.79 vs 2.29; p < 0.04) cells was significantly reduced in the SF compared to PB. There was no difference in the frequency of regulatory T cells. Patients receiving methotrexate had fewer Th2 cells, whereas the Childhood Health Assessment Questionnaire score had a negative association with the frequency of Treg. Median levels of IL-1ß (p < 0.008), IL-6 (p < 0.0001), and IL-17 (p < 0.0001) were higher in SF than in plasma and levels of TGF-ß were lower (p < 0.001). Levels of IL-21 were similar in SF and plasma, whereas IL-23 was undetectable.Conclusion.In patients with ERA, peripheral blood Th1, Th2, Th17, and Treg cells were unchanged, but Th1 and Th17 cells were increased and Th2 cells were reduced in the SF compared to blood. Elevated IL-1ß and IL-6 in SF may be responsible for increased Th17 cells.

scholarly journals Frequencies of CD4+ T Regulatory Cells and their CD25high and FoxP3high Subsets Augment in Peripheral Blood of Patients with Acute and Chronic Brucellosis

2014 ◽  
Vol 5 (3) ◽  
pp. 161-168 ◽  
Author(s):  
Abbas Bahador ◽  
Jamshid Hadjati ◽  
Niloofar Hassannejad ◽  
Hadi Ghazanfari ◽  
Mohammadreza Maracy ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
T Regulatory Cells ◽  
Regulatory Cells

scholarly journals T regulatory cells in childhood arthritis – novel insights

2013 ◽  
Vol 15 ◽  
Author(s):  
Anne M. Pesenacker ◽  
Lucy R. Wedderburn
Keyword(s):  
T Cells ◽  
Juvenile Idiopathic Arthritis ◽  
Regulatory T Cells ◽  
T Regulatory Cells ◽  
Current Knowledge ◽  
Autoimmune Arthritis ◽  
Regulatory Cells ◽  
New Developments ◽  
Childhood Arthritis ◽  
Recent Developments

In recent years, there have been many new developments in the field of regulatory T cells (Treg), challenging the consensus on their behaviour, classification and role(s) in disease. The role Treg might play in autoimmune disease appears to be more complex than previously thought. Here, we discuss the current knowledge of regulatory T cells through animal and human research and illustrate the recent developments in childhood autoimmune arthritis (juvenile idiopathic arthritis (JIA)). Furthermore, this review summarises our understanding of the fields and assesses current and future implications for Treg in the treatment of JIA.

scholarly journals Regulatory T Cells in Human Autoimmune Thyroid Disease

2006 ◽  
Vol 91 (9) ◽  
pp. 3639-3646 ◽  
Author(s):  
Mónica Marazuela ◽  
María A. García-López ◽  
Nicté Figueroa-Vega ◽  
Hortensia de la Fuente ◽  
Brenda Alvarado-Sánchez ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
T Regulatory Cells ◽  
Mononuclear Cells ◽  
Thyroid Tissue ◽  
T Cell Subsets ◽  
Thyroid Cell ◽  
Regulatory Cells ◽  
Rnase Protection ◽  
Autoimmune Thyroid

Abstract Context: T regulatory cells have a key role in the pathogenesis of autoimmune diseases in different animal models. However, less information is available regarding these cells in human autoimmune thyroid diseases (AITD). Objective: The objective of the study was to analyze different regulatory T cell subsets in patients with AITD. Design: We studied by flow cytometry and immunohistochemistry different T regulatory cell subsets in peripheral blood mononuclear cells (PBMCs) and thyroid cell infiltrates from 20 patients with AITD. In addition, the function of TREG lymphocytes was assessed by cell proliferation assays. Finally, TGF-β mRNA in thyroid tissue and its in vitro synthesis by thyroid mononuclear cells (TMCs) was determined by RNase protection assay and quantitative PCR. Results: PBMCs from AITD patients showed an increased percent of CD4+ lymphocytes expressing glucocorticoid-induced TNF receptor (GITR), Foxp3, IL-10, TGF-β, and CD69 as well as CD69+CD25bright, CD69+TGF-β, and CD69+IL-10+ cells, compared with controls. TMCs from these patients showed an increased proportion of CD4+GITR+, CD4+CD69+, and CD69+ cells expressing CD25bright, GITR, and Foxp3, compared with autologous PBMCs. Furthermore, a prominent infiltration of thyroid tissue by CD69+, CD25+, and GITR+ cells, with moderate levels of Foxp3+ lymphocytes, was observed. The suppressive function of peripheral blood TREG cells was defective in AITD patients. Finally, increased levels of TGF-β mRNA were found in thyroid tissue, and thyroid cell infiltrates synthesized in vitro significant levels of TGF-β upon stimulation through CD69. Conclusions: Although T regulatory cells are abundant in inflamed thyroid tissue, they are apparently unable, in most cases, to downmodulate the autoimmune response and the tissue damage seen in AITD.

Multiple Myeloma Patients Treated with Allogeneic Stem Cell Transplantation Show an Increased Frequency of Bone Marrow-Residing CD4+Foxp3+ T Regulatory Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5206-5206
Author(s):  
Djordje Atanackovic ◽  
Yanran Cao ◽  
Christiane Faltz ◽  
Katrin Bartels ◽  
Christine Wolschke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
T Regulatory Cells ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Regulatory Cells

Abstract BACKGROUND: Immunosuppressive CD4+Foxp3+ T regulatory cells (Treg) play a vital role in immune regulation. Thus, Treg contribute to the prevention of autoimmune disease and graft-versus-host reactions following allogeneic stem cell transplantation (alloSCT) but also to the inhibition of effective anti-tumor T cell responses. It has previously been suggested that the frequency of Treg is increased in the peripheral blood of patients with multiple myeloma (MM). However, little is known about the presence of Treg in the bone marrow and it is unclear whether allogeneic stem cell transplantation might deplete Treg from this immune compartment. METHODS: In the present study, we analyzed percentages of CD4+Foxp3+ Treg as well as Treg expression of CD45RA and CCR7 in the bone marrow (BM) and in the peripheral blood of MM patients who had received alloSCT (N=42), in newly diagnosed MM patients (N=18), and in healthy controls (N=15) using flow cytometry. In addition, we performed inhibition assays in order to test the functional relevance of peripheral and BM-residing Treg. RESULTS: While newly diagnosed MM patients and healthy controls showed no significant difference in the proportions of CD4+Foxp3+ Treg in the bone marrow, percentages of BM-residing CD4+Foxp3+ T regulatory cells were markedly higher (p<0.001 and p<0.01) in patients post alloSCT (3.3±0.3%) than in normal BM (1.0±0.3%) or in BM of untreated MM patients (1.8±0.4%). In both groups of patients (p<0.05) as well as in the healthy controls (p<0.001) percentages of Treg were higher in the peripheral blood than in the bone marrow. While there were no differences regarding the percentages of peripheral Treg between the remaining groups, patients post alloSCT had higher percentages of peripheral Treg than newly diagnosed patients (5.6±0.8 vs. 3.2±0.7%, p<0.05). More than 90% of these donor-derived peripheral and BM-residing Treg expressed a memory T cell phenotype, being negative for CD45RA and CCR7. Importantly, peripheral as well as BM-residing Treg of patients post alloSCT were capable of inhibiting the proliferation of autologous non-Treg CD4+ T cells. CONCLUSION: Our study demonstrates for the first time an increased frequency of immunosuppressive Treg in the bone marrow of MM patients. Remarkably, in our patients these memory-type Treg were all donor-derived and led to an efficient replenishment of Treg in the periphery. These Treg might be necessary for the prevention of graft-versus-host disease in the transplanted MM patients, however, they might also contribute to the failure of an effective graft-versus-myeloma effect in the majority of the patients.

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