ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Article
- Compensatory relationships determine the impact of TGF-β on the humoral immune response to hepatitis B surface antigen.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Regulatory T cells in the tumour microenvironment.Nature reviews. Cancer · 2025Review
- ICOS/ICOSLG and PD-1 Co-Expression is Associated with the Progression of Colorectal Precancerous- Carcinoma Immune Microenvironment.Journal of inflammation research · 2023Article
- The immune checkpoint ICOSLG is a relapse-predicting biomarker and therapeutic target in infant t(4;11) acute lymphoblastic leukemia.iScience · 2022Article
- Enriched circulating and tumor-resident TGF-βOncoimmunology · 2022Article
- CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice.International journal of molecular sciences · 2021Article
- Dual targeting of CTLA-4 and CD47 on TScience translational medicine · 2021Article
- Higher Frequency and Increased Expression of Molecules Associated with Suppression on T Regulatory Cells from Newborn Compared with Adult Nonhuman Primates.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Immunomodulatory Strategies Targeting Dendritic Cells to Improve Corneal Graft Survival.Journal of clinical medicine · 2020Review
- ICOSFrontiers in immunology · 2020Review
- Dysregulated ICOSExperimental and therapeutic medicine · 2018Article
- Article
- Bioimaging of alloantigen-stimulated regulatory T cells in rat vascularized composite allotransplantation.PloS one · 2018Article
- Inducible T-Cell Co-Stimulator Impacts Chronic Graft-Versus-Host Disease by Regulating Both Pathogenic and Regulatory T Cells.Frontiers in immunology · 2018Article
- High density lipoproteins selectively promote the survival of human regulatory T cells.Journal of lipid research · 2017Article
- Characterization of c-MafScientific reports · 2017Article
- CD275-Independent IL-17-Producing T Follicular Helper-like Cells in Lymphopenic Autoimmune-Prone Mice.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Poxvirus-based active immunotherapy synergizes with CTLA-4 blockade to increase survival in a murine tumor model by improving the magnitude and quality of cytotoxic T cells.Cancer immunology, immunotherapy : CII · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Regulatory T cells (Treg) are crucial for self-tolerance. It has been an enigma that Treg exhibit an anergic phenotype reflected by hypoproliferation in vitro after TCR stimulation but undergo vigorous proliferation in vivo. We report in this study that murine Treg are prone to death but hyperproliferative in vitro and in vivo, which is different from conventional CD4(+)Foxp3(-) T cells (Tcon). During in vitro culture, most Treg die with or without TCR stimulation, correlated with constitutive activation of the intrinsic death pathway. However, a small portion of the Treg population is more sensitive to TCR stimulation, particularly weak stimulation, proliferates more vigorously than CD4(+) Tcon, and is resistant to activation-induced cell death. Treg proliferation is enhanced by IL-2 but is less dependent on CD28-mediated costimulation than that of Tcon. We demonstrate further that the surviving and proliferative Treg are ICOS(+) whereas the death-prone Treg are ICOS(-). Moreover, ICOS(+) Treg contain much stronger suppressive activity than that of ICOS(-) Treg. Our data indicate that massive death contributes to the anergic phenotype of Treg in vitro and suggest modulation of Treg survival as a therapeutic strategy for treatment of autoimmune diseases and cancer.
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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.