International Immunology, Vol. 14, No. 3, 275-286,
March 2002
© 2002 Japanese Society for Immunology
Expression and function of 4-1BB and 4-1BB ligand on murine dendritic cells
1 Departments of 1Immunology, and
2 Thoracic and Cardiovascular Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
3 Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corp., 2-3 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan
4 First Department of Surgery, Tohoku University School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8574, Japan
Correspondence to: H. Yagita
4-1BB (CDw137) and its ligand (4-1BBL) have been implicated in cellular immune responses. To further characterize the expression and function of 4-1BBL, we newly generated an anti-mouse 4-1BBL mAb (TKS-1), which can inhibit the interaction of 4-1BBL with 4-1BB. Flow cytometric analyses using TKS-1 and an anti-mouse 4-1BB mAb indicated that 4-1BB was inducible on both CD4+ and CD8+ splenic T cells by stimulation with immobilized anti-CD3 mAb, but 4-1BBL was not expressed on resting or activated T cells. 4-1BBL expression was inducible on splenic B cells by stimulation with anti-IgM antibody plus anti-CD40 mAb, on peritoneal macrophages by stimulation with lipopolysaccharide (LPS) and on splenic dendritic cells (DC) by stimulation with anti-CD40 mAb or LPS. Interestingly, splenic DC expressed 4-1BB constitutively, which was down-regulated by anti-CD40 stimulation. Co-culture of splenic DC with 4-1BBL-transfected cells or 4-1BBL-expressing tumor cell lines led to cytokine (IL-6 and IL-12) production and co-stimulatory molecule up-regulation by splenic DC, indicating that 4-1BBL can directly activate DC. Moreover, IL-12 production by anti-CD40-stimulated DC was partially inhibited by TKS-1. These results suggest that 4-1BB expressed on DC may be involved in DC activation through DC–tumor interaction and DC–DC interaction.
Keywords: co-stimulatory molecules, dendritic cells, tumor immunity
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