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

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

Kerstin A Sauer, Joachim H Maxeiner, Roman Karwot, Petra Scholtes, Hans A Lehr, Mark Birkenbach, Richard S Blumberg, Susetta Finotto

J Immunol. 2008 Nov 1;181(9):6148-57.

PMID: 18941205

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413345	EBI-3 from mouse			Price

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