ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2015
Negative CD4 + TIM-3 signaling confers resistance against cold preservation damage in mouse liver transplantation.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Activation of circulating γδ T cells in pediatric IgA vasculitis nephritis links the IL-17 A+ subset to renal risk.Scientific reports · 2026Article
- Mouse orthotopic liver transplantation: Challenges, achievements, and applications.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Review
- T Cell CEACAM1-TIM-3 Crosstalk Alleviates Liver Transplant Injury in Mice and Humans.Gastroenterology · 2023Article
- CD4Antioxidants & redox signaling · 2023Review
- Immune response associated with ischemia and reperfusion injury during organ transplantation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- CD4 T-Cell Exhaustion: Does It Exist and What Are Its Roles in Cancer?Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Review
- Understanding, predicting and achieving liver transplant tolerance: from bench to bedside.Nature reviews. Gastroenterology & hepatology · 2020Review
- Heme Oxygenase-1 in liver transplant ischemia-reperfusion injury: From bench-to-bedside.Free radical biology & medicine · 2020Review
- Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury.The Journal of clinical investigation · 2020Article
- PACAP neuropeptide promotes Hepatocellular Protection via CREB-KLF4 dependent autophagy in mouse liver Ischemia Reperfusion Injury.Theranostics · 2020Article
- A Soluble Form of P Selectin Glycoprotein Ligand 1 Requires Signaling by Nuclear Factor Erythroid 2-Related Factor 2 to Protect Liver Transplant Endothelial Cells Against Ischemia-Reperfusion Injury.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Article
- Innate Immune Regulations and Liver Ischemia-Reperfusion Injury.Transplantation · 2016Review
- Mesenchymal stem cells improve mouse non-heart-beating liver graft survival by inhibiting Kupffer cell apoptosis via TLR4-ERK1/2-Fas/FasL-caspase3 pathway regulation.Stem cell research & therapy · 2016Article
- T Cell Cosignaling Molecules in Transplantation.Immunity · 2016Review
- Liver transplantation in the mouse: Insights into liver immunobiology, tissue injury, and allograft tolerance.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2016Review
- Differential Expression of Immune Checkpoint Modulators on In Vitro Primed CD4(+) and CD8(+) T Cells.Frontiers in immunology · 2016Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Ischemia-reperfusion injury (IRI), an innate immunity-driven local inflammation, remains the major problem in clinical organ transplantation. T cell immunoglobulin and mucin domain (TIM-3)-Galectin-9 (Gal-9) signaling regulates CD4+ Th1 immune responses. Here, we explored TIM-3-Gal-9 function in a clinically relevant murine model of hepatic cold storage and orthotopic liver transplantation (OLT). C57BL/6 livers, preserved for 20 h at 4°C in UW solution, were transplanted to syngeneic mouse recipients. Up-regulation of TIM-3 on OLT-infiltrating activated CD4+ T cells was observed in the early IRI phase (1 h). By 6 h of reperfusion, OLTs in recipients treated with a blocking anti-TIM-3 Ab were characterized by: (1) enhanced hepatocellular damage (sALT levels, liver Suzuki's histological score); (2) polarized cell infiltrate towards Th1/Th17-type phenotype; (3) depressed T cell exhaustion markers (PD-1, LAG3); and (4) elevated neutrophil and macrophage infiltration/activation. In parallel studies, adoptive transfer of CD4+ T cells from naïve WT, but not from TIM-3 Tg donors, readily recreated OLT damage in otherwise IR-resistant RAG(-/-) test recipients. Furthermore, pre-treatment of mice with rGal-9 promoted hepatoprotection against preservation-association liver damage, accompanied by enhanced TIM-3 expression in OLTs. Thus, CD4+ T cell-dependent "negative" TIM-3 costimulation is essential for hepatic homeostasis and resistance against IR stress in OLTs.
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