The NKG2D receptor on NK cells can recognize a variety of ligands on the tumor cell surface. Using a mouse renal cancer (Renca), we show that NKG2D recognition by NK cells was crucial for their ability to limit tumor metastases in vivo in both liver and lungs using perforin-dependent effector mechanisms. However, for the R331 cell line established from Renca, NKG2D recognition and perforin-dependent lysis played no role in controlling liver metastases.
View Article and Find Full Text PDFOur previous studies have identified mechanisms by which cytokine production, blocked by Ly49G2 receptor cross-linking, can be overridden. In this study we analyzed the regulation of other ITAM-positive receptor signaling on NK, NKT, and T cells and characterized the biochemical pathways involved in this signaling. Our studies demonstrate that cross-linking of NKG2D and NK1.
View Article and Find Full Text PDFIn the present study, we have tested the ability of hydrodynamically delivered IL-2 cDNA to modulate the number and function of murine leukocyte subsets in different organs and in mice of different genetic backgrounds, and we have evaluated effects of this mode of gene delivery on established murine tumor metastases. Hydrodynamic administration of the IL-2 gene resulted in the rapid and transient production of up to 160 ng/ml IL-2 in the serum. The appearance of IL-2 was followed by transient production of IFN-gamma and a dramatic and sustained increase in NK cell numbers and NK-mediated cytolytic activity in liver and spleen leukocytes.
View Article and Find Full Text PDFThe technique of bulk cultivation of aged mouse spleen cells in high concentration of IL-2 was employed to obtain NK/LAK cells in sufficient number and enrichment for studies on the effects of aging on their functions. The yield and enrichment were equivalent to that of young mouse spleen cells. The aged and young mouse NK/LAK cells were equivalent also in their functional competence to proliferate, kill target cells and produce IFNgamma; i.
View Article and Find Full Text PDFNKT and NK cells are important immune regulatory cells. The only efficient means to selectively stimulate NKT cells in vivo is alpha-galactosylceramide (alphaGalCer). However, alphaGalCer effectively stimulates and then diminishes the number of detectable NKT cells.
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