scholarly journals The potential of CD4+ regulatory T cells for the therapy of autoimmune diseases

2019 ◽  
pp. 66-69
Author(s):  
A.V. Churov ◽  
A.I. Siutkina ◽  
K.Y. Mamashov ◽  
E.K. Oleinik
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Adverse Events ◽  
Autoimmune Diseases ◽  
Considerable Progress ◽  
Great Promise ◽  
Serious Adverse Events ◽  
Self Tolerance ◽  
Technical Issues

Despite the considerable progress in the therapy of autoimmune pathologies, the existing methods are associated with the risk of serious adverse events. We think that regulatory T cells hold great promise for the therapy of disorders caused by a breakdown in immunological self-tolerance. This article aims at estimating the possible challenges facing Treg-based clinical approaches and offers solutions to the technical issues associated with the use of these cells in the therapy of autoimmune diseases.

scholarly journals Taking regulatory T cells into medicine

2021 ◽  
Vol 218 (6) ◽  
Author(s):  
Shimon Sakaguchi
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Self Tolerance

Regulatory T cells (Tregs) are indispensable for the establishment and maintenance of immunological self-tolerance. Their genetic anomalies or variations in function are causative of various monogenic and polygenic autoimmune diseases. Treg-based reestablishment of self-tolerance is envisioned to cure autoimmune diseases in the clinic.

scholarly journals Restoring self-tolerance in autoimmune diseases by enhancing regulatory T-cells

2019 ◽  
Vol 339 ◽  
pp. 41-49 ◽  
Author(s):  
Prabhakaran Kumar ◽  
Shikha Saini ◽  
Saad Khan ◽  
Swarali Surendra Lele ◽  
Bellur S. Prabhakar
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Self Tolerance

scholarly journals The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities

2021 ◽  
Vol 11 ◽  
Author(s):  
Fatemeh Bayati ◽  
Mahsa Mohammadi ◽  
Maryam Valadi ◽  
Saeid Jamshidi ◽  
Arron Munggela Foma ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Peripheral Tolerance ◽  
Forkhead Box ◽  
Self Tolerance ◽  
Challenges And Opportunities ◽  
Reactive Lymphocytes

Regulatory T cells (Tregs) are an immunosuppressive subgroup of CD4+ T cells which are identified by the expression of forkhead box protein P3 (Foxp3). The modulation capacity of these immune cells holds an important role in both transplantation and the development of autoimmune diseases. These cells are the main mediators of self-tolerance and are essential for avoiding excessive immune reactions. Tregs play a key role in the induction of peripheral tolerance that can prevent autoimmunity, by protecting self-reactive lymphocytes from the immune reaction. In contrast to autoimmune responses, tumor cells exploit Tregs in order to prevent immune cell recognition and anti-tumor immune response during the carcinogenesis process. Recently, numerous studies have focused on unraveling the biological functions and principles of Tregs and their primary suppressive mechanisms. Due to the promising and outstanding results, Tregs have been widely investigated as an alternative tool in preventing graft rejection and treating autoimmune diseases. On the other hand, targeting Tregs for the purpose of improving cancer immunotherapy is being intensively evaluated as a desirable and effective method. The purpose of this review is to point out the characteristic function and therapeutic potential of Tregs in regulatory immune mechanisms in transplantation tolerance, autoimmune diseases, cancer therapy, and also to discuss that how the manipulation of these mechanisms may increase the therapeutic options.

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 THU0051 LOW-DOSE INTERLEUKIN-2 SELECTIVELY EXPAND AND ACTIVATE REGULATORY T CELLS ACROSS 13 AUTOIMMUNE DISEASES.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 237.1-238
Author(s):  
M. Rosenzwajg ◽  
R. Lorenzon ◽  
P. Cacoub ◽  
F. Pitoiset ◽  
S. Aractingi ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Inflammatory Disease ◽  
Low Dose ◽  
Therapeutic Potential ◽  
Interleukin 2 ◽  
Clinical Effects ◽  
Research Support ◽  
Open Label

Background:Regulatory T cells (Tregs) prevent autoimmunity and control inflammation. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential for any autoimmune or inflammatory disease (AIID). We performed a disease-finding “basket trial” (TRANSREGNCT01988506) in patients affected by one of 11 different AIID and reported the outcome of the first 46 patients (Rosenzwajg et al, ARD 2019).Objectives:Here we analyzed and discussed results from deep immunophenotyping, of 78 patients, to comprehensively study the effect of ld-IL2 on the immune system of patients affected by various AIIDMethods:We performed a prospective, open label, phase I-IIa study in 78 patients with a mild to moderate form of one of 13 selected AIID. All patients received ld-IL2 (1 million IU/day) for 5 days, followed by fortnightly injections for 6 months. Deep immunophenotyping was performed before and after 5 days of ld-IL2.Results:ld-IL2 significantly expands both memory Tregs as well as naïve Tregs, including recent thymic emigrant Tregs. It also activates Tregs as demonstrated by the significantly increased expression of HLA-DR, CD39, CD73, GITR, CTLA-4. Similar results were observed across the different AIID.Conclusion:ld-IL2 “universally” improves Treg fitness across 13 autoimmune and inflammatory disease.References:[1]Rosenzwajg M#, Lorenzon R#, Cacoub P, Pham HP, Pitoiset F, El Soufi K, RIbet C, Bernard C, Aractingi S, Banneville B, Beaugerie L, Berenbaum F, Champey J, Chazouilleres O, Corpechot C, Fautrel B, Mekinian A, Regnier E, Saadoun D, Salem JE, Sellam J, Seksik P, Daguenel-Nguyen A, Doppler V, Mariau J, Vicaut E, Klatzmann D. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann Rheum Dis. 2019 Feb;78(2):209-217. doi: 10.1136/annrheumdis-2018-214229. Epub 2018 Nov 24.Disclosure of Interests:Michelle Rosenzwajg: None declared, Roberta Lorenzon: None declared, Patrice cacoub: None declared, Fabien Pitoiset: None declared, Selim Aractingi: None declared, Beatrice Banneville Speakers bureau: Lilly, Novartis, Laurent Beaugerie: None declared, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Julien Champey: None declared, Olivier Chazouilleres: None declared, Christophe Corpechot: None declared, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Arsene Mekinian: None declared, Elodie Regnier: None declared, david Saadoun: None declared, Joe-Elie Salem: None declared, Jérémie SELLAM: None declared, Philippe Seksik: None declared, David Klatzmann Consultant of: ILTOO Pharma

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