These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Negative CD4 + TIM-3 signaling confers resistance against cold preservation damage in mouse liver transplantation.
    Author: Liu Y, Ji H, Zhang Y, Shen XD, Gao F, Nguyen TT, Shang X, Lee N, Busuttil RW, Kupiec-Weglinski JW.
    Journal: Am J Transplant; 2015 Apr; 15(4):954-964. PubMed ID: 25676534.
    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.
    [Abstract] [Full Text] [Related] [New Search]