Article: article from journal or magazin.
Immunosurveillance of lung melanoma metastasis in EBI-3-deficient mice mediated by CD8+ T cells.
Journal of Immunology
EBV-induced gene 3 (EBI-3) codes for a soluble type I receptor homologous to the p40 subunit of IL-12 that is expressed by APCs following activation. In this study, we assessed the role of EBI-3 in a model of lung melanoma metastasis. Intravenous injection of the B16-F10 cell line resulted in a significant reduction of lung tumor metastasis in EBI-3(-/-) recipient mice compared with wild-type mice. The immunological finding accompanying this effect was the expansion of a newly described cell subset called IFN-gamma producing killer dendritic cells associated with CD8(+) T cell responses in the lung of EBI-3(-/-) mice including IFN-gamma release and TNF-alpha-induced programmed tumor cell death. Depletion of CD8(+) T cells as well as targeting T-bet abrogated the protective effects of EBI-3 deficiency on lung melanoma metastases. Finally, adoptive transfer of EBI-3(-/-) CD8(+) T cells into tumor bearing wild-type mice inhibited lung metastasis in recipient mice. Taken together, these data demonstrate that targeting EBI-3 leads to a T-bet-mediated antitumor CD8(+) T cell responses in the lung.
Animals, CD8-Positive T-Lymphocytes, Cell Line, Transformed, Cell Line, Tumor, Cell Transformation, Neoplastic, Cytotoxicity, Immunologic, Gene Knockout Techniques, Immunologic Surveillance, Injections, Intravenous, Lung Neoplasms, Melanoma, Experimental, Mice, Mice, Inbred C57BL, Mice, Knockout, Neoplasm Transplantation, Receptors, Cytokine, T-Box Domain Proteins
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