ArticleJournal of autoimmunity2013
Differential targeting of IL-2 and T cell receptor signaling pathways selectively expands regulatory T cells while inhibiting conventional T cells.
Article in Journal of autoimmunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Whole-genome resequencing reveals genetic diversity and selection signatures of Tongjiang and five goat breeds.Frontiers in veterinary science · 2025Article
- Concomitant use of interleukin-2 and tacrolimus suppresses follicular helper T cell proportion and exerts therapeutic effect against lupus nephritis in systemic lupus erythematosus-like chronic graft versus host disease.Frontiers in immunology · 2024Article
- Skin-derived TSLP stimulates skin migratory dendritic cells to promote the expansion of regulatory T cells.European journal of immunology · 2023Article
- Mitochondrial-regulated Tregs: potential therapeutic targets for autoimmune diseases of the central nervous system.Frontiers in immunology · 2023Review
- Membrane-bound IL-2 improves the expansion, survival, and phenotype of CAR Tregs and confers resistance to calcineurin inhibitors.Frontiers in immunology · 2022Article
- The Future of Regulatory T Cell Therapy: Promises and Challenges of Implementing CAR Technology.Frontiers in immunology · 2020Review
- Low-dose interleukin-2 as a modulator of Treg homeostasis after HSCT: current understanding and future perspectives.International journal of hematology · 2018Review
- Skin-derived TSLP systemically expands regulatory T cells.Journal of autoimmunity · 2017Article
- Impact of Immune-Modulatory Drugs on Regulatory T Cell.Transplantation · 2016Review
- Gene Therapy for Autoimmune Disease.Clinical reviews in allergy & immunology · 2015Review
- New Immunosuppressive Therapies in Uveitis Treatment.International journal of molecular sciences · 2015Review
- IL2-IL21 gene cluster polymorphism is not associated with allograft function after kidney transplantation.International urology and nephrology · 2014Article
- Hand transplants and the mandate for tolerance.Current opinion in organ transplantation · 2014Review
- Unique topics and issues in rheumatology and clinical immunology.Clinical reviews in allergy & immunology · 2014Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Strategies to expand regulatory T cells hold therapeutic potential for ameliorating T cell-mediated autoimmunity. Recently, we reported that the requirements for T cell receptor signaling in conventional T cell and regulatory T cell proliferation are different. Using mutant mice that display defective T cell receptor-mediated phospholipase Cγ (PLCγ) activation, we hereby demonstrate that PLCγ activation is required for antigen-specific conventional T cell proliferation but not for IL-2-induced regulatory T cell proliferation. This led us to hypothesize that in conjunction with IL-2, pharmacological inhibition of T cell receptor-mediated PLCγ activation might offer a novel therapeutic strategy to expand regulatory T cells while simultaneously inhibiting conventional T cell proliferation. Indeed, using the calcineurin inhibitor Cyclosporine A to inhibit signaling downstream of PLCγ, we found that Cyclosporine A attenuated antigen-specific Tconv proliferation but permitted IL-2-induced regulatory T cell expansion in vitro and in vivo. Furthermore, the combination of Cyclosporine A and IL-2 was superior over either Cyclosporine A or IL-2 monotherapy in protection against the T cell-mediated demyelinating autoimmune disease mouse model, experimental autoimmune encephalomyelitis. Thus, a combination of TCR signaling inhibition and IL-2 might be a beneficial strategy in expanding regulatory T cells and inhibiting conventional T cell proliferation in autoimmune settings.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.