2018
DOI: 10.1136/annrheumdis-2018-214229
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Abstract: ObjectiveRegulatory T cells (Tregs) prevent autoimmunity and control inflammation. Consequently, any autoimmune or inflammatory disease reveals a Treg insufficiency. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential.AimWe aimed to assess this potential and select diseases for further clinical development by cross-investigating the effects of ld-IL2 in a single clinical trial treating patients with 1 of 11 autoimmune diseases.MethodsWe performed a prospective, … Show more

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Cited by 280 publications
(199 citation statements)
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“…Because of the critical role for IL-2 in Treg cell homeostasis, IL-2 has also been considered in the treatment of autoimmunity (Sharabi et al, 2018). Administration of IL-2 to mice (alone or as an IL-2-anti-IL-2 antibody complex to increase its bioavailability) and humans can promote the expansion Treg cells in the periphery, and low dose IL-2 has been tested in hepatitis C-related vasculitis, graft-versus-host disease, and multiple autoimmune diseases, resulting in increased Treg cells (Koreth et al, 2011;Rosenzwajg et al, 2019;Saadoun et al, 2011;von Spee-Mayer et al, 2016); multiple trials are underway in subjects with autoimmune disease (NCT01988506, NCT03312335, NCT02424396, NCT02411253).…”
Section: G C Family Cytokines and Translational Advancesmentioning
confidence: 99%
“…Because of the critical role for IL-2 in Treg cell homeostasis, IL-2 has also been considered in the treatment of autoimmunity (Sharabi et al, 2018). Administration of IL-2 to mice (alone or as an IL-2-anti-IL-2 antibody complex to increase its bioavailability) and humans can promote the expansion Treg cells in the periphery, and low dose IL-2 has been tested in hepatitis C-related vasculitis, graft-versus-host disease, and multiple autoimmune diseases, resulting in increased Treg cells (Koreth et al, 2011;Rosenzwajg et al, 2019;Saadoun et al, 2011;von Spee-Mayer et al, 2016); multiple trials are underway in subjects with autoimmune disease (NCT01988506, NCT03312335, NCT02424396, NCT02411253).…”
Section: G C Family Cytokines and Translational Advancesmentioning
confidence: 99%
“…IL2 in high doses is clinically approved as a cancer therapy because of the desired anti-tumor effects of Teffs. The same molecule in low doses preferentially expands and activates Tregs without affecting the Teffs and seems to represent a promising and safe treatment option in patients with various diseases where inflammation is thought to play a pivotal role, such as in various autoimmune diseases [21,23,44,45], graft-versus-host disease [46] and atherosclerosis [47,48]. In this study, IL2 gene delivery led to a sustained expansion of CD4 + CD25 + FoxP3 + Tregs, at the same time leaving Teffs unaffected, suggesting that the strategy of using rAAV-induced IL2 production probably resembles lowdose IL2 therapy in patients.…”
Section: Resultsmentioning
confidence: 99%
“…Tregs constitutively express the IL2 receptor (IL2R) and although they do not produce IL2 themselves, they are dependent on IL2 for their peripheral homeostasis and maintenance [16,17]. Administration of low-dose IL2 tips the balance between Tregs and T effector cells (Teffs) towards Tregs [18] showing great promise for the treatment of autoimmune disorders [19][20][21][22][23]. Despite these successes, little is known of how the presence of low-dose IL2 and the consequent expansion of Tregs could affect beneficial effector immune responses when patients receiving the treatment develop acute bacterial infections, such as S. aureus arthritis.…”
Section: Introductionmentioning
confidence: 99%
“…Moreover, IL-2 might cause severe toxicity, when administered in high-doses, yet in lower doses the therapeutic effect is unsatisfactory [188]. This can be at least partially explained by the results of clinical trials concerning autoimmune diseases which demonstrated that low doses of IL-2 specifically activated and expanded Tregs [189][190][191]. Another tested approach was based on adoptive transfer of genetically modified IL-2-secreting TILs, but it also did not increase their in vivo persistence or therapeutic effectiveness [192].…”
Section: Stimulation Of T Cells With Cytokinesmentioning
confidence: 99%