Expression and function of 4-1BB and 4-1BB ligand on murine dendritic cells

• Published in: International immunology 2002-03, Vol.14 (3), p.275-286
• Main Authors: Futagawa, Toshiro, Akiba, Hisaya, Kodama, Tomohiro, Takeda, Kazuyoshi, Hosoda, Yasuyuki, Yagita, Hideo, Okumura, Ko
• Format: Article
• Language: English
• Subjects: 4-1BB Ligand; Animals; Antibodies, Monoclonal - immunology; Antigens, CD; AP alkaline phosphatase; B-Lymphocytes - immunology; CD40 Antigens - metabolism; Cells, Cultured; co-stimulatory molecules; CTL cytotoxic T lymphocyte; DC dendritic cell; dendritic cells; Dendritic Cells - immunology; Female; GM-CSF granulocyte macrophage colony stimulating factor; Interleukin-12 - biosynthesis; L ligand; LPS lipopolysaccharide; Macrophages - immunology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred Strains; Mice, Transgenic; PE phycoerythrin; Receptors, Nerve Growth Factor - genetics; Receptors, Nerve Growth Factor - metabolism; Receptors, Nerve Growth Factor - physiology; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor - physiology; T-Lymphocytes - immunology; TNF tumor necrosis factor; tumor immunity; Tumor Necrosis Factor Receptor Superfamily, Member 9; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/14.3.275

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.