scholarly journals In vitro induction of T regulatory cells by a methylated CpG DNA sequence in humans: Potential therapeutic applications in allergic and autoimmune diseases

2018 ◽  
Vol 39 (2) ◽  
pp. 143-152 ◽  
Author(s):  
Oliver J. Lawless ◽  
Joseph A. Bellanti ◽  
Milton L. Brown ◽  
Kathryn Sandberg ◽  
Jason G. Umans ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Dna Sequence ◽  
T Regulatory Cells ◽  
Regulatory Cells ◽  
Cpg Dna ◽  
Therapeutic Applications ◽  
In Vitro Induction

Expanding Tregs with IVIg

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 481-482 ◽  
Author(s):  
Rachel R. Caspi
Keyword(s):  
Autoimmune Diseases ◽  
Mechanism Of Action ◽  
T Regulatory Cells ◽  
Regulatory Cells

In this issue of Blood, Ephrem et al demonstrate that IVIg expands CD4+CD25+FoxP3+ T regulatory cells (Tregs) and enhances their function in vivo and in vitro. Their findings shed new light on the elusive mechanism of action of IVIg in ameliorating autoimmune diseases.

scholarly journals BDC12-4.1 T-Cell Receptor Transgenic Insulin-Specific CD4 T Cells Are Resistant to In Vitro Differentiation into Functional Foxp3+ T Regulatory Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112242 ◽  
Author(s):  
Ghanashyam Sarikonda ◽  
Georgia Fousteri ◽  
Sowbarnika Sachithanantham ◽  
Jacqueline F. Miller ◽  
Amy Dave ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
T Regulatory Cells ◽  
Cell Receptor ◽  
Regulatory Cells ◽  
In Vitro Differentiation

scholarly journals Phosphoantigen-activated Vγ2Vδ2 T cells antagonize IL-2–induced CD4+CD25+Foxp3+ T regulatory cells in mycobacterial infection

Blood ◽  
2009 ◽  
Vol 113 (4) ◽  
pp. 837-845 ◽  
Author(s):  
Guangming Gong ◽  
Lingyun Shao ◽  
Yunqi Wang ◽  
Crystal Y. Chen ◽  
Dan Huang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Treatment Regimen ◽  
T Regulatory Cells ◽  
Mycobacterial Infection ◽  
T Cell Subsets ◽  
Regulatory Cells ◽  
Ifn Γ ◽  
Vγ2vδ2 T Cells

Abstract Although Foxp3+ T regulatory cells (Tregs) are well documented for their ability to suppress various immune cells, T-cell subsets capable of counteracting Tregs have not been demonstrated. Here, we assessed phosphoantigen-activated Vγ2Vδ2 T cells for the ability to interplay with Tregs in the context of mycobacterial infection. A short-term IL-2 treatment regimen induced marked expansion of CD4+CD25+Foxp3+ T cells and subsequent suppression of mycobacterium-driven increases in numbers of Vγ2Vδ2 T cells. Surprisingly, activation of Vγ2Vδ2 T cells by adding phosphoantigen Picostim to the IL-2 treatment regimen down-regulated IL-2–induced expansion of CD4+CD25+Foxp3+ T cells. Consistently, in vitro activation of Vγ2Vδ2 T cells by phosphoantigen plus IL-2 down-regulated IL-2–induced expansion of CD4+CD25+Foxp3+ T cells. Interestingly, anti–IFN-γ–neutralizing antibody, not anti–TGF-β or anti–IL-4, reduced the ability of activated Vγ2Vδ2 T cells to down-regulate Tregs, suggesting that autocrine IFN-γ and its network contributed to Vγ2Vδ2 T cells' antagonizing effects. Furthermore, activation of Vγ2Vδ2 T cells by Picostim plus IL-2 treatment appeared to reverse Treg-driven suppression of immune responses of phosphoantigen-specific IFNγ+ or perforin+ Vγ2Vδ2 T cells and PPD-specific IFNγ+αβ T cells. Thus, phos-phoantigen activation of Vγ2Vδ2 T cells antagonizes IL-2–induced expansion of Tregs and subsequent suppression of Ag-specific antimicrobial T-cell responses in mycobacterial infection.

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.

Level and characteristics of natural T regulatory cells in vascular-connective autoimmune diseases

2007 ◽  
Vol 74 (2) ◽  
pp. S215
Author(s):  
Leontina Banica ◽  
Alina Besliu ◽  
Gina Pistol ◽  
Crina Stavaru ◽  
Ruxandra Ionescu ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
T Regulatory Cells ◽  
Regulatory Cells

scholarly journals Can Cinnamon Spice Down Autoimmune Diseases?

2020 ◽  
Vol 5 (6) ◽  
Keyword(s):  
Autoimmune Diseases ◽  
Th17 Cells ◽  
T Regulatory Cells ◽  
Urea Cycle ◽  
Autoimmune Disorders ◽  
Food Additive ◽  
Regulatory Cells ◽  
Cycle Disorders ◽  
And Function ◽  
Nonketotic Hyperglycinemia

Autoimmune diseases are one of the dreadful group of human diseases that have always been of keen interest to researchers. Due to complex and broad-spectrum nature, scientists are not yet able to pinpoint the pathogenesis of and delineate effective therapy against this group of diseases. However, it is becoming clear that a decrease in number and function of T regulatory cells (Treg), an increase in autoreactive Th1/Th17 cells and associated immunomodulation and inflammation participate in the pathogenesis of many autoimmune diseases. Cinnamon (Cinnamonum verum or Cinnamonum cassia) is a widely used natural spice and flavoring ingredient and its metabolite sodium benzoate (NaB) is a food-additive and FDA-approved drug against nonketotic hyperglycinemia (NKH) and urea cycle disorders (UCD). Recent studies indicate that cinnamon either in powder or extract form and NaB are capable of modulating different autoimmune pathways as well as protecting animals from different autoimmune disorders. Here, we have made an honest attempt to delineate such pieces of evidence with available anti-autoimmune mechanisms and analyze whether cinnamon supplements could be used to control the fury of autoimmune disorders.

scholarly journals Μελέτη της in vitro κυτταρολυτικής δραστικότητας των ΝΚ - κυττάρων ασθενών πασχόντων από μυελικές κακοήθειες

2019 ◽  
Author(s):  
Μαρία Τσιρογιάννη
Keyword(s):  
T Regulatory Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Regulatory Cells

Στην παρούσα προοπτική μελέτη εκτιμήθηκε η συσχέτιση μεταξύ της ΝΚ κυτταροτοξικής δραστικότητας, των Μυελικών Κατασταλτικών κυττάρων (Myeloid Derived Suppressor cells - MDSCs) και των Τ-ρυθμιστικών κυττάρων (T-Regulatory cells – Tregs), ως προς τη διάρκεια της ανταπόκρισης και την ολική επιβίωση, ασθενών πασχόντων απο υψηλού κινδύνου Μυελοδυσπλαστικό σύνδρομο (ΜΔΣ) ή ολιγοβλαστική Οξεία Μυελογενή Λευχαιμία (ΟΜΛ) που λάμβαναν θεραπεία με τον υπομεθυλιωτικό παράγοντα 5-Αζασυτιδίνη. Ο απώτερος σκοπός της μελέτης ήταν η αναγνώριση πρώϊμων βιοδεικτών με προγνωστική σημασία ως προς την συνολική ανταπόκριση των ασθενών αυτών στη χορηγούμενη θεραπεία.Οι ασθενείς που συμμετείχαν στην παρούσα μελέτη είχαν ήδη λάβει τουλάχιστον τρείς κύκλους θεραπείας με τον υπομεθυλιωτικό παράγοντα 5-Αζασυτιδίνη. Η in vitro προσδιορισμένη ΝΚ-κυτταροτοξικότητα σε αυτή την ομάδα των ασθενών έχει προγνωστική αξία ως προς τη διάρκεια της ανταπόκρισης και ως προς την ολική επιβίωση, οι ασθενείς που επιδείκνυαν υψηλή ΝΚ-κυτταροτοξικότητα παρουσίαζαν μακρύτερη επιβίωση και μακρύτερη διάρκεια ανταπόκρισης σε σύγκριση με τους ασθενείς που επιδείκνυαν χαμηλή ΝΚ-κυτταροτοξικότητα. Οι πληθυσμοί των ανοσορρυθμιστικών κυττάρων MDSCs και Tregs στο περιφερικό αίμα ασθενών μετα βραχεία έκθεση σε 5-Αζασυτιδίνη, δε διέφεραν στατιστικώς σημαντικά σε σύγκριση με τον πληθυσμό των υγιών μαρτύρων.Σύμφωνα με τα αποτελέσματα της μελέτης μας, η θεραπευτική δράση της 5-Αζασυτιδίνης διενεργείται, τουλάχιστον μερικώς, μέσω ανοσορρυθμιστικής επίδρασης του παράγοντα αυτού. Με βάση την πρόσφατη αναζήτηση της βιβλιογραφίας, η μελέτη αυτή αποτελεί την πρώτη δημοσιευμένη μελέτη που καταγράφει θετική συσχέτιση μεταξύ της ΝΚ-κυτταροτοξικότητας και της ολικής επιβίωσης ασθενών υπο 5-Αζασυτιδίνη.

Adenosine A2A Receptor Agonist Mediated Prevention of Graft-Versus Host Disease In the Mouse Is Associated with An Increase of T-Regulatory Cells In Target Organs.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3744-3744
Author(s):  
Kyu Lee Han ◽  
Sherry Walker ◽  
Harry L. Malech ◽  
Elizabeth M. Kang
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Acute Gvhd ◽  
T Regulatory Cells ◽  
Treated Group ◽  
Regulatory Cells ◽  
High Power Field ◽  
Target Organs ◽  
A2ar Agonist

Abstract Abstract 3744 Graft versus host disease (GVHD) is a serious complication of allogenic hematopoietic stem cell transplantation (HSCT) affecting primarily the liver, intestine, skin and lymphoid organs. T-regulatory cells (Tregs) are a subset of T cells that are characterized by CD4+CD25high and express the Foxp3 transcription factor. There is increasing recognition that Tregs likely are important in preventing development, reducing the severity and/or mediating resolution of GVHD. It has been reported that giving donor Tregs will suppress development of GVHD in a mouse model; however it is not clear whether the immunologic suppression by Tregs occurs in the target organs. Agonists of the Gs-coupled Adenosine A2A receptor (A2AR) agonists have been demonstrated to terminate inflammation and improve survival in solid organ transplant ischemia models. We previously have reported that the A2AR specific agonist, ATL146e, also can decrease the incidence and severity of GVHD as well as improve survival of mice in a GVHD transplant mouse model. In this same GVHD mouse model, ATL146e treatment increases the number of donor derived CD4+CD25highFoxp3+ Tregs. In order to further understand the role of the agonist in GVHD abrogation we performed studies looking at A2AR agonist mediated appearance of Tregs in the target organs affected by GVHD in this model. Using a parental into irradiated F1 offspring transplant model (C57BL/6J [B6, H-2b] -> B6D2F1/J [BDF1, H-2b/d]) we can induce GVHD as manifested by weight loss and mortality in 100% of mice by infusing an additional 10 million donor T cells into mice previously engrafted with 10 million bone marrow donor cells using 850cGy conditioning. We administered the A2AR specific agonists, ATL1223 or ATL370, or a PBS control by osmotic mini pumps resulting in continuous subcutaneous infusion for 14 days starting one day before the donor T cell infusion. Mice that received only the donor bone marrow transplant and not the additional donor T cells did not develop GVHD and served as an additional control. We collected ear and colon biopsies from the transplanted mice to assess these target organs (skin and gut) usually affected by GVHD in this model. Tissue was obtained, placed in 10% formalin and paraffin embedded and stained by immunohistochemistry (IHC) for intracellular FoxP3 by incubating overnight with 1:200 mouse anti-mouse/human/rat—FoxP3 IgG. The slides were washed and then incubated with anti-mouse IgG conjugated to Tetramethylrhodamine (TRITC). We then counted the number of Foxp3+ cells per high power field. We also examined whether specific agonist activation of A2AR can increase the number of Tregs in vitro by culturing CD4+ CD25− cells in the presence of either TGF-beta and/or the A2AR specific agonists. As in our previous studies with the specific A2AR agonist ATL146e, the agonists ATL1223 and ATL370 also were effective at preventing the acute GVHD syndrome of weight loss and mortality seen in the PBS treated controls. Treatment with these agonists resulted in an increase in CD4+CD25+FoxP3+ Tregs in the spleen compared to the PBS treated group at days 14 to 20 after HSCT. In addition we were able to document significant increases in the number of Foxp3 positive T lymphocytes infiltrating skin and colon compared to the PBS treated group. The number of Foxp3+ T cells per high power field was 14 ± 6 in the control and 64 ± 14 in the A2AR agonist treated mice (p = 0.0281). Finally from our in vitro data we also observed a 4.2 to 5.4 fold increase in the number of Foxp3+ Tregs in vitro after A2AR activation compared to TGF beta treatment only. Thus we have confirmed that the specific activation of A2AR inhibits acute GVHD through the increase of donor-derived CD4+ CD25+ FoxP3+ immunosuppressive T regulatory cells in vivo and in vitro. Furthermore, our histological observation suggests the possibility that increased Tregs by treatment with A2AR specific agonist is responsible for suppressing the immune response in GVHD target tissues. Therefore, our observation provides additional mechanistic basis for the anti-inflammatory capacity of A2AR agonist in acute GVHD. Additional studies are ongoing to further elucidate the mechanism by which A2AR specific agonist increases Tregs. Disclosures: No relevant conflicts of interest to declare.

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