Immunosurveillance of Lung Melanoma Metastasis in EBI-3-Deficient Mice Mediated by CD8+ T Cells

• Published in: The Journal of immunology (1950) 2008-11, Vol.181 (9), p.6148-6157
• Main Authors: Sauer, Kerstin A, Maxeiner, Joachim H, Karwot, Roman, Scholtes, Petra, Lehr, Hans A, Birkenbach, Mark, Blumberg, Richard S, Finotto, Susetta
• Format: Article
• Language: English
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; Cell Line, Transformed; Cell Line, Tumor; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - immunology; Cell Transformation, Neoplastic - pathology; Cytotoxicity, Immunologic - genetics; Gene Knockout Techniques; Immunologic Surveillance - genetics; Injections, Intravenous; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Melanoma, Experimental - immunology; Melanoma, Experimental - metabolism; Melanoma, Experimental - secondary; Melanoma, Experimental - therapy; Mice; Mice, Inbred C57BL; Mice, Knockout; Minor Histocompatibility Antigens; Neoplasm Transplantation; Receptors, Cytokine - deficiency; Receptors, Cytokine - genetics; Receptors, Cytokine - physiology; T-Box Domain Proteins - deficiency; T-Box Domain Proteins - genetics; T-Box Domain Proteins - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.181.9.6148

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.