Enhancement of NKT Cells and Increase in Regulatory T Cells Results in Improved Allograft Survival

Li, Wei; Carper, K.; Perkins, James D.

doi:10.1016/j.jss.2006.03.025

Cited by 5 publications

(1 citation statement)

References 63 publications

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“…Most of them are CD1d restricted, which is a non-classical MHC I molecule presenting lipids to NKT cells [13] . Once activated, NKT cells can rapidly secrete IFN-␥ and IL-4 [14] , which activate downstream NK cells, DCs, B and CD8+ T cells [13] to inhibit tumors [15,16] , fight infections [17,18] and prolong allotransplant survival [19][20][21] . However, the role of NKT cells in tumor xenograft survival differs in different models [3,4,[22][23][24] .…”

Section: Introductionmentioning

confidence: 99%

Prolonged Survival of Human Hepatocarcinoma Cells in the Liver of Newborn C57BL/6 Mice and Resulting Cellular Xenorejection, Especially the Activation of Hepatic Natural Killer T Cells

Bai

Zhang

et al. 2010

Pathobiology

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Objective: To investigate the fate of human hepatocellular carcinoma (HCC) in the livers of newborn mice and the resulting cellular rejection.Methods: 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. Results: 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. Conclusion: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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