ArticleCell death & disease2016
A novel differentiation pathway from CD4⁺ T cells to CD4⁻ T cells for maintaining immune system homeostasis.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- IFITM1 enhances anti-tumor function of unconventional TCRαβ double negative T cells by upregulating mitophagy.Science China. Life sciences · 2026Article
- Molecular mechanisms underlying T cell subset imbalance and precision therapeutic targets in primary biliary cholangitis.Frontiers in pharmacology · 2026Review
- Article
- RELB Reprograms Exhausted Tumor-Infiltrating Lymphocytes for Improved Adoptive Cell Therapy.bioRxiv : the preprint server for biology · 2025Article
- Double-negative T cells in combination with ursodeoxycholic acid ameliorates immune-mediated cholangitis in mice.BMC medicine · 2025Article
- Purinergic signaling by TCRαβScience bulletin · 2025Article
- IL-33 promotes double negative T cell survival via the NF-κB pathway.Cell death & disease · 2023Article
- The Critical and Diverse Roles of CD4Cellular and molecular gastroenterology and hepatology · 2022Article
- CD3Frontiers in immunology · 2022Review
- CD4 derived double negative T cells prevent the development and progression of nonalcoholic steatohepatitis.Nature communications · 2021Article
- Double negative T cells mediate Lag3-dependent antigen-specific protection in allergic asthma.Nature communications · 2019Article
- The Role of Systems Biologic Approach in Cell Signaling and Drug Development Responses-A Mini Review.Medical sciences (Basel, Switzerland) · 2018Review
- Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells.Cell death & disease · 2018Article
- The hypoxic tumour microenvironment.Oncogenesis · 2018Review
- EGCG Maintains Th1/Th2 Balance and Mitigates Ulcerative Colitis Induced by Dextran Sulfate Sodium through TLR4/MyD88/NF-Canadian journal of gastroenterology & hepatology · 2017Article
- Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice.Journal of translational medicine · 2016Article
- Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD4(+) T lymphocytes are key players in the adaptive immune system and can differentiate into a variety of effector and regulatory T cells. Here, we provide evidence that a novel differentiation pathway of CD4(+) T cells shifts the balance from a destructive T-cell response to one that favors regulation in an immune-mediated liver injury model. Peripheral CD4(-)CD8(-)NK1.1(-) double-negative T cells (DNT) was increased following Concanavalin A administration in mice. Adoptive transfer of DNT led to significant protection from hepatocyte necrosis by direct inhibition on the activation of lymphocytes, a process that occurred primarily through the perforin-granzyme B route. These DNT converted from CD4(+) rather than CD8(+) T cells, a process primarily regulated by OX40. DNT migrated to the liver through the CXCR3-CXCL9/CXCL10 interaction. In conclusion, we elucidated a novel differentiation pathway from activated CD4(+) T cells to regulatory DNT cells for maintaining homeostasis of the immune system in vivo, and provided key evidence that utilizing this novel differentiation pathway has potential application in the prevention and treatment of autoimmune diseases.
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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.