ArticleProceedings of the National Academy of Sciences of the United States of America2013
Construction of self-recognizing regulatory T cells from conventional T cells by controlling CTLA-4 and IL-2 expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 110 citations in OpenAlex.
- Review
- Galectin-3 exacerbates autoimmune diabetes by limiting regulatory T cell differentiation and function.Science advances · 2026Article
- Role of Treg cells in diabetes mellitus and association with traditional Chinese medicine: a literature review.Frontiers in immunology · 2026Review
- Regulatory T cell memory: implications for malaria.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- Regulatory T cell therapy for Graft-versus-Host Disease.Bone marrow transplantation · 2025Review
- Immunosuppressive cells in acute myeloid leukemia: mechanisms and therapeutic target.Frontiers in immunology · 2025Review
- Regulatory T cell dysfunction and immunotherapeutic breakthroughs in type 1 diabetes.Frontiers in endocrinology · 2025Review
- Current trends in sensitizing immune checkpoint inhibitors for cancer treatment.Molecular cancer · 2024Review
- Mini-Review: Tregs as a Tool for Therapy-Obvious and Non-Obvious Challenges and Solutions.Cells · 2024Review
- Peripheral-derived regulatory T cells contribute to tumor-mediated immune suppression in a nonredundant manner.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Regulatory T Cells for Control of Autoimmunity.Advances in experimental medicine and biology · 2024Article
- Regulatory T cells in autoimmune kidney diseases and transplantation.Nature reviews. Nephrology · 2023Review
- In Vitro Analysis of CTLA-4-Mediated Transendocytosis by Regulatory T Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- A new target of radiotherapy combined with immunotherapy: regulatory T cells.Frontiers in immunology · 2023Review
- Distinct disease-specific Tfh cell populations in 2 different fibrotic diseases: IgGThe Journal of allergy and clinical immunology · 2022Article
- Untangling the Knots of Regulatory T Cell Therapy in Solid Organ Transplantation.Frontiers in immunology · 2022Review
- Induction of stable human FOXP3Immunology and cell biology · 2021Article
- Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Structural analogues in herbal medicine ginseng hit a shared target to achieve cumulative bioactivity.Communications biology · 2021Article
- Thymus and autoimmunity.Seminars in immunopathology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thymus-produced CD4(+) regulatory T (Treg) cells, which specifically express the transcription factor forkhead box p3, are potently immunosuppressive and characteristically possess a self-reactive T-cell receptor (TCR) repertoire. To determine the molecular basis of Treg suppressive activity and their self-skewed TCR repertoire formation, we attempted to reconstruct these Treg-specific properties in conventional T (Tconv) cells by genetic manipulation. We show that Tconv cells rendered IL-2 deficient and constitutively expressing transgenic cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) were potently suppressive in vitro when they were preactivated by antigenic stimulation. They also suppressed in vivo inflammatory bowel disease and systemic autoimmunity/inflammation produced by Treg deficiency. In addition, in the thymus, transgenic CTLA-4 expression in developing Tconv cells skewed their TCR repertoire toward higher self-reactivity, whereas CTLA-4 deficiency specifically in developing thymic Treg cells cancelled their physiological TCR self-skewing. The extracellular portion of CTLA-4 was sufficient for the suppression and repertoire shifting. It interfered with CD28 signaling to responder Tconv cells via outcompeting CD28 for binding to CD80 and CD86,or modulating CD80/CD86 expression on antigen-presenting cells. Thus, a triad of IL-2 repression, CTLA-4 expression, and antigenic stimulation is a minimalistic requirement for conferring Treg-like suppressive activity on Tconv cells, in accordance with the function of forkhead box p3 to strongly repress IL-2 and maintain CTLA-4 expression in natural Treg cells. Moreover, CTLA-4 expression is a key element for the formation of a self-reactive TCR repertoire in natural Treg cells. These findings can be exploited to control immune responses by targeting IL-2 and CTLA-4 in Treg and Tconv cells.
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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.