ArticleBlood2007
New differentiation pathway for double-negative regulatory T cells that regulates the magnitude of immune responses.
Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 125 citations in OpenAlex.
- Tumor-infiltrated double-negative regulatory T cells predict outcome of T cell-based immunotherapy in nasopharyngeal carcinoma.Cell reports. Medicine · 2025Trial
- Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade.Blood · 2019Trial
- Characterization of circulating CD4International journal of hematology · 2017Trial
- IFITM1 enhances anti-tumor function of unconventional TCRαβ double negative T cells by upregulating mitophagy.Science China. Life sciences · 2026Article
- Double negative T cells (CD4Frontiers in immunology · 2026Article
- Dual inhibition of CSF-1R and IDO modulates the fibrotic and immunosuppressive tumor microenvironment in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Article
- Increased CD95Frontiers in immunology · 2026Article
- Hepatic Arachidonic Acid Dysregulation Impairs Double-Negative Regulatory T Cell-Mediated Immunoregulation via CD39 Downregulation and Drives MASLD Development.Journal of immunology research · 2026Article
- Antigen-Specifically Activated CD8+ and Double-Negative T Cells Accumulate in the Brain of Alzheimer's Disease Mice.Aging and disease · 2025Article
- Double-negative T cells in combination with ursodeoxycholic acid ameliorates immune-mediated cholangitis in mice.BMC medicine · 2025Article
- Characterization and effective expansion of CD4Molecular therapy. Methods & clinical development · 2025Article
- Purinergic signaling by TCRαβScience bulletin · 2025Article
- CD3Frontiers in immunology · 2025Review
- CD4-Derived Double-Negative T Cells Ameliorate Alzheimer's Disease-Like Phenotypes in the 5×FAD Mouse Model.CNS neuroscience & therapeutics · 2025Article
- Double-negative T cells in pediatric rheumatic diseases.Clinical and experimental pediatrics · 2024Article
- Immune profiling analysis of double-negative T cells in patients with systemic sclerosis.Clinical rheumatology · 2024Article
- Double-negative T cells ameliorate psoriasis by selectively inhibiting IL-17A-producing γδJournal of translational medicine · 2024Article
- Autoimmune CD8+ T cells in type 1 diabetes: from single-cell RNA sequencing to T-cell receptor redirection.Frontiers in endocrinology · 2024Review
- Circulating T cells: a promising biomarker of anti-PD-(L)1 therapy.Frontiers in immunology · 2024Review
- Canine peripheral non-conventional TCRαβFrontiers in immunology · 2024Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have demonstrated that in peripheral lymphoid tissues of normal mice and healthy humans, 1% to 5% of alphabeta T-cell receptor-positive (TCR(+)) T cells are CD4(-)CD8(-) (double-negative [DN]) T cells, capable of down-regulating immune responses. However, the origin and developmental pathway of DN T cells is still not clear. In this study, by monitoring CD4 expression during T-cell proliferation and differentiation, we identified a new differentiation pathway for the conversion of CD4(+) T cells to DN regulatory T cells. We showed that the converted DN T cells retained a stable phenotype after restimulation and that furthermore, the disappearance of cell-surface CD4 molecules on converted DN T cells was a result of CD4 gene silencing. The converted DN T cells were resistant to activation-induced cell death (AICD) and expressed a unique set of cell-surface markers and gene profiles. These cells were highly potent in suppressing alloimmune responses both in vitro and in vivo in an antigen-specific manner. Perforin was highly expressed by the converted DN regulatory T cells and played a role in DN T-cell-mediated suppression. Our findings thus identify a new differentiation pathway for DN regulatory T cells and uncover a new intrinsic homeostatic mechanism that regulates the magnitude of immune responses. This pathway provides a novel, cell-based, therapeutic approach for preventing allograft rejection.
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What OpenQuestion holds
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.