自然杀伤性T细胞
细胞毒性T细胞
CD8型
生物
移植
免疫学
癌症研究
免疫系统
医学
体外
内科学
生物化学
作者
Xiumin Du,Zengliang Bai,Jing‐Ping Zhang,Lanlan Liu,Ying Han,Ze Wang,Tianxiao Huan,Biao Wu
出处
期刊:Pathobiology
[S. Karger AG]
日期:2010-01-01
卷期号:77 (3): 115-128
被引量:2
摘要
<i>Objective:</i> To investigate the fate of human hepatocellular carcinoma (HCC) in the livers of newborn mice and the resulting cellular rejection.<i>Methods:</i> Two HCC cell lines (HepG2 and HCCLM3) labeled with DMAHAS were orthotopically transplanted to newborn and adult mice with or without low-dose cyclosporin A (CsA) treatment (10 mg/kg). The fate of tumor xenografts was examined and the resulting cellular response was investigated. <i>Results:</i> Tumor xenografts survived in newborn mice for >4 weeks, with a delayed lymphocyte infiltration mediated by CD4+ T, CD8+ T and NK1.1+ cells. In contrast, the xenografts survived in adults <8–10 days with an acute cellular rejection by CD8+T cells, NK1.1+ cells, macrophages or neutrophils. Orthotopic transplantation of human HCC xenografts elicited a strong cytotoxic response in newborn mice (p < 0.05), and selective T/NK1.1+ cell deletion in vitro suggested that such effector cells were mainly CD8+ T cells. Moreover, tumor xenografts induced a rapid activation of hepatic natural killer T (NKT) cells in both newborn and adult mice with enhanced secretion of IL-4 and IFN-γ in serum and subsequent NKT-like cytotoxicity. The rapid activation of NKT cells could be efficiently suppressed by low-dose CsA treatment, possibly in a CD1d-independent manner. <i>Conclusion:</i>Our data suggest that the livers of newborn mice were more suitable for the survival of xenografts than those of adult mice. Cell-mediated tumor xenorejection in newborn mice was different from that in adults, and hepatic NKT cells may play an important role in early tumor xenorejection.
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